Design of fused systems based on σh-adducts of 6-nitro-1,2,4- triazolo[1,5-a]pyrimidine with π-excessive heteroaromatic compounds

Article abstract of DOI:10.1007/s11172-009-0172-6

A new method was developed for the construction of tetra- and pentacyclic fused systems based on σH-adducts of 6-nitro-1,2,4-triazolo[1,5-a] pyrimidine with π-excessive heteroaromatic compounds. The method involves the reduction of the nitro group accompa

Full text of DOI:10.1007/s11172-009-0172-6

Russian Chemical Bulletin, International Edition, Vol. 58, No. 6, pp. 1309—1314, June, 2009
1309
Н
Design of fused systems based on σ ꢀadducts of
6ꢀnitroꢀ1,2,4ꢀtriazolo[1,5ꢀa]pyrimidine with
πꢀexcessive heteroaromatic compounds
E. B. Gorbunov,a G. L. Rusinov,a O. N. Chupakhin,a,b and V. N. Charushina,b
aI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 741189. Eꢀmail: chupakhin@ios.uran.ru
bUral State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation
A new method was developed for the construction of tetraꢀ and pentacyclic fused systems
H
based on σ ꢀadducts of 6ꢀnitroꢀ1,2,4ꢀtriazolo[1,5ꢀa]pyrimidine with πꢀexcessive heteroaromatic
compounds. The method involves the reduction of the nitro group accompanied by the aromaꢀ
tization of the dihydropyrimidine ring and followed by the cyclocondensation of the amino
derivative with aldehydes.
H
Key words: 6ꢀnitroꢀ1,2,4ꢀtriazolo[1,5ꢀa]pyrimidine, σ ꢀadducts, nitro group reduction,
aromatization.
Scheme 1
Main methods of chemical modifications of πꢀdeficient
arenes and hetarenes, which are used also for the conꢀ
struction of fused systems, involve the nucleophilic subꢀ
stitution reactions of good leaving groups Le = Hal, NR2,
OR, OSO2R, etc. (Scheme 1, path A). One of limitations
of the SNAr reactions (more precisely, SNipsoAr) is that it is
necessary to introduce a good leaving group Le into the
substrate molecule for this reaction to occur.
In the last decades, the reactions based on the direct
nucleophilic attack on the unsubstituted carbon atom
Csp2—H of the (hetero)aromatic ring were actively develꢀ
oped as the individual synthetic methodology.1—3 These
reactions are usually completed with the substitution
H
of hydrogen (SN reactions) or are stopped at the step of
W is an electronꢀwithdrawing group, Le is a good leaving
group, and Nu is a nucleophilic reagent.
formation of σHꢀadducts (AN reactions) (Scheme 1).
σHꢀAdducts essentially differ in the stability. Thus,
both unstable adducts, which are spectroscopically
detected only at low temperatures and which readily
undergo aromatization, and very stable preparatively isoꢀ
lated compounds are known. Among the latter are, in
particular, Cꢀadducts of nitro derivatives of azoloazines
6—10 (Scheme 2).3—6 Attempts to transform these dihydro
compounds into aromatic systems under the action of
classical hydride acceptors, such as oxygen, dichloroꢀ
dicyanobenzoquinone, triphenylmethyl tetrafluoroborate,
etc., failed. The use of stronger oxidizing agents (for
example, potassium permanganate) leads to the destrucꢀ
tion of the molecule.
(sodium dithionite, tin chloride, iron hydroxide, catalytic
hydrogenation). The reduction of the nitro group is acꢀ
companied by the unexpected, on the first glance, dehyꢀ
drogenation of the dihydropyrimidine ring. This provides
H
an approach to SN products 11—15 not through the
conventional oxidation of the dihydropyrimidine moiety
to the pyrimidine moiety followed by the transformation
of the nitro group into the amino group but through the
concerted process, which apparently involves the elimiꢀ
nation of water from the intermediate A (Scheme 3).
This seemingly paradoxical reductive dehydrogenaꢀ
tion has a general character and can be used for particular
synthetic purposes. The vicinal arrangement of the amino
group and π-excessive heterocycles opens new possibiliꢀ
Previously, we have briefly reported4,5 on the unusual
aromatization of σHꢀadducts 6 under reducing conditions
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1272—1277, June, 2009.
1066ꢀ5285/09/5806ꢀ1309 © 2009 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
Gorbunov et al.
Scheme 2
centers (the amino group and the carbon atoms of the π-
excessive heterocycle) and can be involved in reactions
with various electrophilic agents.
The aim of the present study was to develop the aboveꢀ
mentioned synthetic potential and to use it for the design
of fused heterocyclic systems based on aromatic aminoꢀ
pyrimidines 11—15 containing fragments of π-excessive
heteroaromatic compounds by the reactions with aldeꢀ
hydes. As a continuation of the research on the reductive
dehydrogenation of compounds 6,4 we studied a series of
σHꢀadducts 7—10. These dihydro compounds are formed
in high yields as stable brightꢀcolored crystalline subꢀ
stances. It was found that, regardless of the structure
of the azole moiety of the molecules, the reduction of
the nitro group in adducts 6—10 is accompanied by
the aromatization of the pyrimidine ring (see Scheme 2,
Tables 1 and 2).
Thus, the reduction of the nitro group in adducts
6—10 with sodium dithionite in aqueous ammonia
affords 6ꢀaminoꢀ7ꢀhetarylazolo[1,5ꢀa]pyrimidines 11—15.
The acidꢀcatalyzed condensation of amine 11a containꢀ
ing the pyrrole moiety with aldehydes is not stopped at
the formation of azomethine and proceeds further to give
tetracyclic system 16 as the final product. In the case of
amine 11b containing the Nꢀmethylpyrrole moiety, comꢀ
pound 17 was chromatographically detected. However, in
the course of isolation, the dihydropyridine fragment is
oxidized by atmospheric oxygen to give aromatic products
18a—c (Scheme 4). The structures of the latter products
were confirmed by the 1H NMR spectra of compounds 16
and 17 (see the Experimental section) and by the Xꢀray
diffraction data for compound 16a (Fig. 1).
Compound
1
2
3
4
5
6a—f, 11a—f
7, 12
8, 13
9, 14
10, 15
X
N
N
N
Y
CH
N
C—SMe
CH
C—CN
CH
Z
N
N
N
N
C—COOEt
N
N
N
C—CN
N
N
N
N
C—SMe
CH
C—CN
N
N
C—COOEt
N
C—CN
Nu
=
(6a, 11a),
(6b, 11b),
(6c, 11c),
(6d, 11d),
(6e,
Amine 11c containing the thiophene moiety does not
undergo heterocyclization; the reaction with benzaldeꢀ
hyde is stopped at the formation of the corresponding
azomethine 19.
7—10, 11e, 12—15),
(6f, 11f)
Some of compounds synthesized according to the
aboveꢀdescribed scheme can be of interest for biological
tests, because these compounds are structurally similar to
alkaloids, and azepinoindole derivatives are known to serve
as ligands of dopamine receptors.7
ties for the cyclization, the annulation, and the design of
polycyclic systems. In particular, amines 11—15 have preꢀ
requisites for the construction of tetraꢀ and pentacyclic
heterosystems because they contain several nucleophilic
Scheme 3
C(13)
C(12)
C(3)
N(3)
C(4)
N(2)
C(14)
С(11)
С(16)
C(2)
C(1)
N(4)
C(5)
C(15)
C(6)
C(7)
N(1)
N(6)
C(10)
C(9)
С(8)
N(5)
Fig. 1. Molecular structure of 16a. Displacement ellipsoids are
drawn at the probability level p = 50%.

Design of σHꢀadducts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
1311
1
Table 1. H NMR spectra (DMSOꢀd6)
Compound
δ (J/Hz)
7
8
9
12.40 (s, 1 Н, NH); 11.23 (s, 1 Н, NH); 8.50 (s, 1 Н, С(5)Н); 7.50 (d, 1 Н, J = 2.8); 7.37—7.29 (m, 3 Н, С(7)Н, Ar);
7.09—7.06 (m, 1 Н); 7.00—6.97 (m, 1 Н)
12.42 (s, 1 Н, NH); 11.20 (s, 1 Н, NH); 8.51 (s, 1 Н, С(5)Н); 7.54 (d, 1 Н, J = 2.8); 7.36—7.29 (m, 3 H, С(7)Н, Ar);
7.04—7.02 (m, 1 H); 7.00—6.96 (m, 1 H); 2.36 (s, 3 H, СН3)
11.21 (s, NH); 10.89 (s, NH); 8.26 (s, 1 H, С(5)Н); 7.12 (s, 1 H, С(2)Н); 7.49 (d, 1 Н, СН, J = 2.8); 7.36—7.30
(m, 2 H, Ar); 7.09—7.05 (m, 1 H, Ar); 6.99—6.95 (m, 1 H, Ar); 6.91 (s, 1 H, С(7)Н); 4.30—4.25 (q, 2 H, СН2,
J = 7.0); 1.28 (t, 3 H, СН3, J = 7.1)
10
12
13
14
12.43 (s, 1 H, NH); 11.35 (s, 1 H, NH); 8.44 (s, 1 H, С(5)Н); 7.59 (d, 1 H, J = 2.8); 7.39 (d, 1 H, J = 8); 7.14—7.06
(m, 3 H, С(7)Н, Ar); 6.98—6.94 (m, 1 H)
12.10 (s, 1 H, NH); 8.67 (s, 1 H, С(5)Н); 8.60—8.58 (m, 1 H); 8.56 (d, 1 H, J = 2.8); 7.57 (m, 1 H); 7.31—7.25
(m, 2 H); 5.66 (s, 2 H, NH2)
11.93 (s, 1 H, NH); 8.54 (s, 1 H, С(5)Н); 8.05 (d, 1 H, J = 2.8); 7.53 (d, 1 H, J = 8); 7.21—7.17 (m, 1 H); 7.10—7.06
(m, 1 H, Ar); 5.04 (s, 2 H, NH2); 2.55 (s, 3 H, СН3)
11.89 (s, 1 H, NH); 8.60 (s, 1 H, С(5)Н); 8.29 (s, 1 H, С(2)Н); 7.97 (d, 1 H, J = 2.8); 7.53 (d, 1 H, Ar, J = 8);
7.25—7.18 (m, 2 H, Ar); 7.08—7.04 (m, 1 H, Ar); 5.12 (s, 2 H, NH2); 4.30—4.25 (q, 2 H, СН2, J = 7.1); 1.31 (t, 3 H,
СН3, J = 7.1)
15
11.94 (s, 1 H, NH); 8.72 (s, 1 H, С(5)Н); 7.84 (d, 1 H, J = 2.8); 7.55 (d, 1 H, Ar, J = 8); 7.26—7.21 (m, 2 H, Ar);
7.08—7.05 (m, 1 H, Ar); 5.48 (s, 2 H, NH2)
16a
8.58 (s, 1 H, С(5)Н); 8.53 (s, 1 H, С(2)Н); 7.51—7.46 (m, 2 H, Ph); 7.42—7.40 (m, 3 H, Ph); 7.33—7.30 (two dd,
2 Н, pyrrol, J1 = 3.8, J2 = 1.5); 6.96—6.73 (dd, 1 H, pyrrol, J1 = 3, J2 = 1.5); 6.72 (d, 1 H, NH, J = 2); 6.49—6.48 (dd,
1 Н, С(7)H, J1 = 3.8, J2 = 2.5)
16b
16c
8.55 (s, 1 H, С(5)Н); 8.52 (s, 1 H, С(2)Н); 7.37—7.32 (two dd, 2 H, pyrrol, J1 = 3.8, J2 = 1.5); 6.86 (d, 1 H, NH,
J = 2); 6.46—6.44 (dd, 1 H, pyrrol, J1 = 3.8, J2 = 2); 5.62—5.60 (dt, 1 H, С(7)H, J1 = 5.8, J2 =3.2); 1.86—1.83 (m,
2 H, СН2); 1.23—0.88 (m, 10Н); 0.78 (t, 3 H, СН3, J = 6.7)
8.69 (s, 1 H, С(5)Н); 8.55 (s, 1 H, С(2)Н); 7.38—7.36 (two dd, 2 H, pyrrol, J1 = 3.8, J2 = 1.5); 6.48—6.46 (dd, 1 H,
pyrrol, J1 = 3.8, J2 = 1.4); 5.64 (t, 1 H, С(7)H, J = 5.8); 1.86—1.83 (m, 2 H, СН2); 1.26—1.17 (m, 16 H); 0.84 (t, 3 H,
СН3, J = 6.7)
18a
18b
18c
19
9.54 (s, 1 H, С(5)Н); 8.78 (s, 1 H, С(2)Н); 8.04—8.01 (m, 3 H, pyrrol, Ph); 7.65—7.59 (m, 3 H, Ph); 7.10 (d, 1 H,
pyrrol, J = 2.8); 4.72 (s, 3 H, CH3)
9.45 (s, 1 H, С(5)Н); 8.75 (s, 1 H, С(2)Н); 7.96 (d, 1 H, pyrrol, J = 2.8); 7.13 (d, 1 H, pyrrol, J = 2.8); 4.69 (s, 3 H,
СН3), 3.19 (t, 2 H, CH2, J = 7.6); 1.88—1.84 (m, 2 H, СН2); 1.41—1.15 (m, 10 Н); 0.85 (t, 3 H, СН3, J = 6.9)
9.44 (s, 1 H, С(5)Н); 8.75 (s, 1 H, С(2)Н); 7.93 (d, 1 H, pyrrol, J = 2.8); 7.14 (d, 1 H, pyrrol, J = 2.8); 4.66 (s, 3 H,
СН3), 3.20 (t, 2 H, CH2, J = 7.0); 1.87—1.84 (m, 2 H, СН2); 1.43—1.15 (m, 10 Н); 0.83 (t, 3 H, СН3, J = 6.8)
9.07—9.06 (m, 1 H, thiophene); 9.05 (s, 1 H, СН); 9.03 (s, 1 H, С(5)Н); 8.82 (s, 1 H, С(2)Н); 8.25—8.23 (dd, 1 H,
thiophene, J1 = 5.1, J2 = 1.2); 8.14—8.12 (m, 2 H, Ph); 7.66—7.63 (m, 3 H, Ph); 7.46—7.44 (m, 1 H, thiophene)
21a
21b
21c
12.39 (s, NH); 9.16 (d, 1 H, С(1)Н, J = 2.8); 8.57 (s, 1 H, С(8)H); 8.53 (s, С(11)H); 7.54 (d, 1 H, Ar, J = 8); 7.23—7.20
(m, 1 H, Ar); 7.14—7.10 (m, 2 H, Ar); 7.06—6.97 (m, 1 H, Ar); 6.92 (d, 2 H, Ar, J = 7.4); 5.76 (s, 1 H, С(6)Н)
9.15 (s, 1 H, С(1)Н); 8.57 (s, 1 H, С(8)H); 8.54 (s, 1 H, С(11)H); 7.63 (d, 1 H, Ar, J = 8); 7.35—7.31 (m, 1 H, Ar);
7.15— 7.11 (m, 2 H, Ar); 7.09—7.03 (m, 1 H, Ar); 6.93 (d, 2 H, Ar, J = 7.4); 5.84 (s, 1 H, С(6)Н), 4.08 (s, 3 H, СН3)
12.42 (s, 1 H, NH); 9.18 (d, 1 H, С(1)Н, J = 3.0); 8.74 (s, 1 H, С(8)H); 8.73 (s, 1 H, С(11)H); 7.47—7.45 (m, 1 H,
Ar); 7.20—7.16 (m, 1 H, Ar); 6.99—6.97 (m, 1 H, Ar); 4.53 (t, 1 H, С(6)Н, J = 6.4); 1.39—1.17 (m, 12 H); 0.81 (t,
3 H, СН3, J = 6.8)
21d
21e
21f
12.43 (s, 1 H, NH); 9.16 (d, 1 H, С(1)Н, J = 3.0); 8.77 (s, 1 H, С(8)H); 8.71 (s, 1 H, С(11)H); 7.48—7.47 (m, 1 H,
Ar); 7.23—7.19 (m, 1 H, Ar); 7.04—7.02 (m, 1 H, Ar); 4.54 (t, 1 H, С(6)Н, J = 6.4); 1.57—1.13 (m, 14 H); 0.80 (t,
3 H, СН3, J = 6.8)
12.50 (s, 1 H, NH); 9.19 (d, 1 H, С(1)Н, J = 3.0); 8.79 (s, 1 H, С(8)H); 8.78 (s, 1 H, С(11)H); 7.49—7.47 (m, 1 H,
Ar); 7.21—7.17 (m, 1 H, Ar); 7.00— 6.99 (m, 1 H, Ar); 4.57 (t, 1 H, С(6)Н, J = 6.5); 1.39—1.31 (m, 2 H, СН2);
1.24—1.06 (m, 16 H); 0.84 (t, 3 H, СН3, J = 6.8)
12.38 (s, 1 H, NH); 9.16 (d, 1 H, С(1)Н, J = 3.0); 8.72 (s, 1 H, С(8)H); 8.68 (s, 1 H, С(11)H); 7.48—7.46 (m, 1 H,
Ar); 7.22—7.18 (m, 1 H, Ar); 7.03—7.01 (m, 1 H, Ar); 4.52 (t, 1 H, С(6)Н, J = 6.4); 1.27—1.13 (m, 14 H); 0.83
(t, 3 H, СН3, J = 6.8)

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
Gorbunov et al.
Scheme 4
Table 2. Melting points, yields, and elemental analysis data
Comꢀ Yield M.p.
pound (%)
Found_
Calculated
Molecular
formula
/оС
C
H
N
7
70
85
87
84
49
44
66
68
69
40
55
50
49
51
61
60
78
62
65
70
58
208—
210
146—
148
238—
240
232—
234
216—
218
188—
190
50.87 3.18
50.89 3.20
51.20 3.66
51.21 3.68
57.79 4.30
57.79 4.28
58.03 2.74
58.01 2.74
57.35 3.60
57.37 3.61
56.77 4.10
56.74 4.08
63.50 4.70
63.54 4.71
64.24 3.00
64.21 3.03
66.60 4.17
66.66 4.20
65.72 7.15
65.78 7.14
68.85 8.27
68.82 8.25
67.97 4.00
67.99 4.03
67.07 6.90
67.06 6.88
69.79 7.98
69.81 7.99
62.92 3.64
62.93 3.63
64.07 4.04
64.09 4.03
64.88 4.41
64.86 4.41
63.54 6.33
63.55 6.35
64.33 6.60
64.30 6.62
64.99 6.87
65.00 6.88
65.66 7.10
65.66 7.12
34.65 С12H9N7O2
34.61
25.62 С14H12N6O2S
25.59
19.83 С17H15N5O4
19.82
29.57 С16H9N7O2
29.59
39.00 С12H9N7
39.02
28.32 С14H12N6S
28.36
21.82 С17H15N5O2
21.79
32.77 С16H9N7
32.76
29.17 С16H12N6
29.15
27.10 С17H22N6
27.07
22.96 С21Н30N6
22.93
27.97 C17H12N6
27.98
26.06 C18H22N6
26.07
22.21 C22H30N6
22.20
22.93 C16H11N5S
22.93
8
9
10
12
13
14
>300
15
230—
232
221—
223
16а
16b
16c
18a
18b
18c
19
Oil
112—
114
256—
258
161—
162
122—
124
198—
200
262—
264
232—
234
162—
164
i. RCHO/HCl. 16—18: Ph (a), C H (b), C
H
(c)
7
15
11 23
The condensation of aminotriazolopyrimidines 11e,f
with aldehydes (Scheme 5) in aprotic solvents affords the
corresponding azomethines capable of forming fused
structures 21 and 22.
21а
21b
21c
21d
21e
21f
22.40 C20H14N6
22.42 •HCl
21.62 C21H16N6
21.61 •HCl
21.18 C21H24N6
21.17 •HCl
20.46 C22H26N6
20.45 •HCl
19.77 C23H28N6
19.78 •HCl
19.13 C24H30N6
19.14 •HCl
It was found that the heterocyclization of 11e,f with
aldehydes in an acidic medium occurs with the involveꢀ
ment of the benzene ring of indole rather than at posiꢀ
tion 2 of the pyrrole ring and affords the only product,
viz., 6ꢀRꢀ1,2,4ꢀtriazolo[1″,2″: 1,2]pyrimido[6´,5´:6,7]ꢀ
azepino[5,4,3ꢀcd]indole (21). This is confirmed by the
168—
170
195—
197
123—
125
1
fact that the H NMR spectra show a oneꢀproton signal
for the atom H(1) (δ = 9.15—9.16), which appears as a
singlet or a doublet depending on the nature of the subꢀ
stituent (R = CH3 or H, respectively). In addition, the
1H NMR spectra show a singlet for H(6), signals of
the threeꢀspin system of the indole moiety, and signals
for aromatic protons. An alternative structure 22 can be
rejected because it is inconsistent with the 1H NMR
spectra. In addition, compound 21d was studied by Xꢀray
diffraction (Fig. 2).
fused systems. The nitro group activates the heterocycle
for the nucleophilic attack and stabilizes σHꢀadducts, and
the reduction of the nitro group results in the initiation of
the aromatization of the ring apparently through the inꢀ
termediate formation of hydroxylamine A.4 Finally, the
transformation of the nitro group into the amino group
provides structural prerequisites for cyclocondensation
reactions.
To sum up, let us note that the nitro group plays a key
role in the aboveꢀconsidered method for the design of

Design of σHꢀadducts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
1313
Scheme 5
spectra were recorded on a Bruker DRXꢀ400 spectrometer
(400 MHz) in [2H6]DMSO with Me4Si as the internal standard.
The elemental analysis was carried out on an automated Carlo
Erba 1108 CHNO analyzer. The melting points were deterꢀ
mined on combined Boetius hot stages and are uncorrected.
The results of the Xꢀray diffraction studies of compounds
16a and 21d were deposited with the Cambridge Crystallographic
Data Centre* (CCDC 731801 for 21d and 731802 for 16a).
Synthesis of 7ꢀ(indolꢀ2ꢀyl)ꢀ6ꢀnitroꢀ4,7ꢀdihydroazoloꢀ
[1,5ꢀa]pyrimidines 7—10 (general method). The corresponding
6ꢀnitroazolo[1,5ꢀa]pyrimidine (1 mmol) and indole (1 mmol)
were refluxed in acetonitrile (3 mL). The solution was cooled,
and the product that precipitated was separated by filtration and
twice washed with diethyl ether.
Synthesis of 6ꢀaminoꢀ7ꢀ(indolꢀ2ꢀyl)azolo[1,5ꢀa]pyrimidines
12—15 (general method). Sodium dithionite (6 mmol) was added
with stirring to a solution of the corresponding adduct 7—10
(1 mmol) in aqueous ammonia (3—5 mL). The reaction mixture
was kept at 60—70°C for 30 min and then at room temperature
for 3—5 h. The product that precipitated was separated by filtraꢀ
tion, washed with water, and crystallized from ethanol.
Synthesis of 7ꢀRꢀ6,7ꢀdihydropyrrolo[1,2ꢀc]ꢀ1,2,4ꢀtriazoloꢀ
[5´,1´:2,3]pyrimido[4,5ꢀe]pyrimidines (16a—c) (general method).
Equivalent amounts of amine 11a and the corresponding
aldehyde were refluxed for 30 min in a 2 M HCl—EtOH mixture
(1 : 4). The reaction mixture was applied on silica gel, and the
product was isolated by column chromatography in a chloroꢀ
form : methanol system (30 : 1) (Rf = 0.8—0.9).
20, 21
R
R´
20, 21
R
R´
Synthesis of 7ꢀsubstituted 10ꢀmethylpyrrolo[2´,3´:4,5]ꢀ
pyrido[2,3ꢀе]ꢀ1,2,4ꢀtriazolo[1,5ꢀa]pyrimidines (18a—c) (general
method). Equivalent amounts of amine 11b and the correspondꢀ
ing aldehyde were refluxed for 30 min in a 2 M HCl—EtOH
mixture (1 : 4). The reaction mixture was applied on silica gel,
and the product was isolated by column chromatography in a
chloroform : methanol system (30 : 1) (Rf = 0.8—0.9).
6ꢀBenzylideneaminoꢀ7ꢀ(thiopenꢀ2ꢀyl)ꢀ1,2,4ꢀtriazolo[1,5ꢀ
a]pyrimidine (19). Amine 11c (0.5 mmol) and benzaldehyde (0.5
mmol) were refluxed in a 2 M HCl—EtOH mixture (1 : 4, 5 mL)
for 30 min. Then the solution was cooled. The product that
precipitated was separated by filtration, washed with ethanol,
and dried in a vacuum desiccator.
Synthesis of 2ꢀRꢀ6ꢀR´ꢀ1,2,4ꢀtriazolo[1″,2″:1,2]pyrimidoꢀ
[6´,5´:6,7]azepino[5,4,3ꢀcd]indoles (21a—f) (general method).
Equivalent amounts of amine 11e or 11f and the corresponding
aldehyde were refluxed for 30 min in a 2 M HCl—EtOH mixture
(2 : 1). The precipitate that formed after cooling was washed
with water, crystallized from aqueous ethanol, and dried in vacuo.
Crystallographic data for compounds 16a and 21d. Single
crystals of compounds 16a and 21d were grown by crystallizaꢀ
tion from EtOH. The Xꢀray diffraction data were collected on a
Xcalibur 3 diffractometer equipped with a CCD detector
(λ(MoKα) = 0.71073, graphite monochromator, ωꢀ and ϕꢀscanꢀ
ning technique, T = 295 K). The structure was solved by direct
methods with the use of the SHELXSꢀ97 program package and
refined by the fullꢀmatrix leastꢀsquares method first isotropically
and then anisotropically using the SHELXLꢀ97 program packꢀ
age. The hydrogen atoms were located in difference electron
density maps and refined using a riding model.
a
b
H
Me
Ph
Ph
d
e
H
H
C H
8
17
19
C H
9
C(11)
C(10)
C(9)
C(12)
C(13)
N(2)
C(8)
C(6)
C(14)
N(1)
C(7)
C(5)
N(3)
C(16)
C(17)
C(18)
C(1)
C(2)
N(4)
C(15)
C(4)
N(6)
C(3)
C(19)
C(20)
N(5)
C(21)
Cl(O1)
C(22)
Fig. 2. Molecular structure of 21d. Displacement ellipsoids are
shown at the probability level p = 50%. The disorder of the alkyl
fragment (see the Experimental section) is not shown.
Experimental
The course of the reactions was monitored and the purity of
the reaction products was checked by TLC on plates with a fixed
Sorbfil layer using a 9 : 1 chloroform—methanol mixture as the
eluent; spots were visualized by UV irradiation. The 1H NMR
* These data can be obtained, free of charge, on application to
www.ccdc.cam.ac.uk/data_request/cif.

1314
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
Gorbunov et al.
Table 3. Xꢀray data collection and structure refinement statistics
We thank P. A. Slepukhin for performing the Xꢀray
diffraction study.
Parameter
21d
16a
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 07ꢀ03ꢀ96123,
05ꢀ03ꢀ33112ꢀa, and 05ꢀ03ꢀ33113ꢀa).
Molecular formula
Molecular weight
Crystal system
Space group
a/Å
b/Å
c/Å
α/deg
β/deg
С22Н27ClN6
410.95
Rhombohedral Orthorhombic
Rꢀ3
31.253(4)
31.253(4)
11.2903(14)
90.00
С16Н12N6
288.32
Pbca
7.5474(15)
14.308(3)
24.448(4)
90.00
90.00
90.00
2640.1(8)
8
1.451
References
1. F. Terrier, in Organic Nitro Chemistry Series, VCH Publishers,
Inc., New York, 1991, 500 pp.
2. O. N. Chupakhin, V. N. Charushin, H. C. van der Plas,
Nucleophilic Aromatic Substitution of Hydrogen, Academic
Press, San Diego, N. Y., 1994, 376 pp.
3. (a) M. Makosza, K. Wojciechowski, Chem. Rev., 2004, 104,
2631; (b) V. L. Rusinov, O. N. Chupakhin, Nitroaziny
[Nitroazines], Novosibirsk, Nauka, 1991 (in Russian).
4. G. L. Rusinov, E. B. Gorbunov, V. N. Charushin, O. N.
Chupakhin, Tetrahedron Lett., 2007, 48, 5873.
5. E. B. Gorbunov, G. L. Rusinov, R. I. Ishmetova, V. N.
Charushin, O. N. Chupakhin, Zh. Org. Khim., 2008, 44, 130
[Russ. J. Org. Chem. (Engl. Transl.), 2008, 44].
6. G. L. Rusinov, P. V. Plekhanov, V. L. Rusinov, O. N.
Chupakhin, G. G. Aleksandrov, Zh. Org. Khim., 1998, 34,
290 [Russ. J. Org. Chem. (Engl. Transl.), 2008, 44].
7. P. Gmeiner, H. Hubner, K. A. Abu Safieh, I. I. Fasfous,
M. M. ElꢀAbadelah, S. S. Sabri, W. Voelter, Heterocycles,
2003, 60, 1339.
90.00
γ/deg
120.00
9550(2)
18
1.286
0.201
V/Å3
Z
dcalc/g cm–3
μ/ mm—1
Scanning range
Number of measured
0.094
26.39 ≥ θ ≥ 2.69 26.37 ≥ θ ≥ 2.97
4178
0
2178
2652
0.0511
1409
reflections (Rint
Number of reflections
with I > 2σ(I)
Number of refined parameters
R1 (based on reflections
with I > 2σ(I))
wR2 (based on reflections )
with I > 2σ(I)
)
384
0.0581
203
0.0508
0.1571
0.1035
R1 (based on all reflections)
wR2 (based on all reflections)
0.1236
0.1739
0.1009
0.1168
In molecule 21d, the alkyl fragment is disordered over three
sites with occupancies of 0.4, 0.3, and 0.3.
The Xꢀray data collection and structure refinement statistics
are given in Table 3.
Received April 7, 2009;
in revised form May 13, 2009