Synthesis and properties of a new fused heterocyclic system 12H-benzo[5,6][1,2,4]triazepino[3,4-a]isoindol-5(6H)-one

Article abstract of DOI:10.1007/s11172-008-0027-6

12H-Benzo[5,6][1,2,4]triazepino[3,4-a]isoindol-5(6H)-one was synthesized by the condensation of anthranilic acid hydrazide with o-phthalaldehyde. The structure of this compound was established by the X-ray diffraction study of its isopropyl derivative. The mechanism of formation of this compound was suggested and its alkylation reactions were investigated.

Full text of DOI:10.1007/s11172-008-0027-6

Russian Chemical Bulletin, International Edition, Vol. 57, No. 1, pp. 186—192, January, 2008
186
Synthesis and properties of a new fused heterocyclic system
12Hꢀbenzo[5,6][1,2,4]triazepino[3,4ꢀa]isoindolꢀ5(6H)ꢀone
L. Yu. Ukhin,a L. G. Kuzґmina,b T. N. Gribanova,a L. V. Belousova,a and Zh. I. Orlovaa

aInstitute of Physical and Organic Chemistry, Rostov State University,
194/2 prosp. Stachki, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863) 243 4776. Eꢀmail: may@ipoc.rsu.ru
bN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 953 1279. Eꢀmail: kuzmina@igic.ras.ru
12HꢀBenzo[5,6][1,2,4]triazepino[3,4ꢀa]isoindolꢀ5(6H)ꢀone was synthesized by the condensaꢀ
tion of anthranilic acid hydrazide with oꢀphthalaldehyde. The structure of this compound was
established by the Xꢀray diffraction study of its isopropyl derivative. The mechanism of formation of
this compound was suggested and its alkylation reactions were investigated.
Key words: anthranilic acid hydrazide, oꢀphthalaldehyde, 12Hꢀbenzo[5,6][1,2,4]triazepiꢀ
no[3,4ꢀa]isoindolꢀ5(6H)ꢀone derivatives.
aldehyde 2 in PriOH was found to afford a crystalline
The reaction of anthranilic acid hydrazide (1) with
brightꢀyellow compound (Scheme 1). The molecular
weight of the product is indicative of the condensation of
compounds 1 and 2 accompanied by the loss of two water
oꢀformylbenzoic acid produces a mixture of two
fused heterocyclic systems, 3,4ꢀbenzoꢀ1,10ꢀdioxoꢀ
1,2,4a,5,10,11ꢀhexahydropyridazino[3,2ꢀb]quinazoline
and 6ꢀaminoꢀ5,6,6a,11ꢀtetrahydroisoindolo[2,1ꢀa]quinꢀ
azolineꢀ5,11ꢀdione.1 Biological assays showed that the
former compound exhibits high analgesic activity.2 The
synthesis of its analogs having high analgesic and antiinꢀ
flammatory activities was documented.2—4
1
molecules. The H NMR spectrum shows, in addition to
signals for aromatic protons, singlets for the NH proton
of hydrazide and the protons of the CH2 group. The
Xꢀray diffraction study demonstrated that the alkylation
of this product with isopropyl iodide gave 12Hꢀ
benzo[5,6]ꢀ6ꢀisopropyl[1,2,4]triazepino[3,4ꢀa]isoindolꢀ
5ꢀone (7c). The possible mechanism of the reaction is
presented in Scheme 1.
It was of interest to study the reaction of hydrazide 1
with oꢀphthalaldehyde (2). To our knowledge, data on
this reaction are lacking in the literature. Heating of 1 with
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 180—185, January, 2008.
1066ꢀ5285/08/5701ꢀ0186 © 2008 Springer Science+Business Media, Inc.

Benzo[1,2,4]triazepine[3,4ꢀa]isoindoleꢀ5ꢀone
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
187
a
b
1.239
1.248
1.417
1.446
1.493
1.417
1.290
1.471
1.391
1.390
1.448
1.239
1.409
1.470
1.414
1.383
1.472
1.477
1.410
1.405
1.296
1.380
1.396
1.409
1.401
1.398
1.390
1.427
1.362
1.418
1.420
1.480
1.429
1.356
1.392
1.405
1.405
1.390
1.425
1.383
1.379
1.233
3a
3b
c
d
1.228
1.240
1.409
1.420
1.428
1.438
1.244
1.478
1.412
1.443
1.235
1.475
1.292
1.408
1.493
1.403
1.287
1.488
1.404
1.384
1.419
1.427
1.363
1.469
1.403
1.473
1.406
1.392
1.381
1.405
1.361
1.423
1.404
1.392
1.394
1.397
1.418
1.393
1.384
1.380
1.395
3c
3d
Fig. 1. Geometric characteristics of the most stable conformers 3a (∆E = 0) (a), 3b (∆E = 0.51) (b), 3c (∆E = 3.56) (c), and 3d (∆E = 7.76) (d)
calculated at the B3LYP/3ꢀ21G* level of theory. The bond lengths are given in Å.
It is known1,5 that the hydrazide NH2 group of comꢀ
pound 1 is the first to react with aldehydes. The reaction
of compound 1 with oꢀcarboxybenzaldehyde at room
temperature produces oꢀcarboxybenzaldehyde oꢀaminoꢀ
benzoylhydrazone. This suggests that the first step of the
reaction of hydrazide 1 with phthalaldehyde also affords
hydrazone 3.
exist as a series of conformational isomers (Fig. 1, Table 1).
Conformer 3a is most stable among these isomers. It is
0.5—7.8 kcal mol–1 energetically more favorable than the
other conformers. The amino group in conformer 3a is
oriented with respect to the C=N bond so that the system
is structurally suitable for further transformation 3→4
(the proton transfer from NH2 to the hydrazone nitrogen
atom and the formation of the new C—N bond). The
transition 3a→4 is exothermic. The aldehyde group in
compound 4 can interact with NH at positions 1 or 3 of
the tetrahydrotriazepine ring. According to calculations,
system 4 also exists as several conformers (Fig. 2), conꢀ
former 4a containing the aldehyde group closely spaced
to N(1) and the rather strong (1.792 Å) N(1)H...O hydroꢀ
gen bond being most stable. Conformer 4b, in which the
aldehyde group points toward the N(3) atom, is
12.2 kcal mol—1 less stable than 4a. Therefore, the interacꢀ
tion between the aldehyde group and NH at position 1
resulting in the transformation into structure 5 is more
favorable. The transition 4a→5 is exothermic (the energy
gain is 7.1 kcal mol–1). Compound 5 undergoes dehydraꢀ
tion as a result of the symmetry allowed 1,5ꢀproton shift.
However, this reaction produces compound 6 with the
nonaromatic isoindole structure, which can be stabilized
by the transformation into 12Hꢀbenzo[5,6][1,2,4]triꢀ
azepino[3,4ꢀa]isoindolꢀ5(6H)ꢀone 7a as a result of the
According to quantum chemical calculations (at the DFT
B3LYP/3ꢀ21G* level of theory),6,7 system
3
can
Table 1. Energy characteristics of systems 3—5 (see Scheme 1)
calculated at the B3LYP/3ꢀ21G* level of theory and corresponding
to the energy minima (λ = 0) on the potential energy surface
~
Structure
–Etot/a.u.
ZPE/a.u.
ω /cm–1
1
3a
3b
3c
3d
4a
4b
4c
5
889.157410
889.156595
889.151733
889.145043
889.168817
889.162211
889.149293
889.180131
0.258080
0.257658
0.257327
0.257096
0.261070
0.260523
0.260097
0.262212
17.6
15.8
35.0
19.8
26.6
25.8
30.7
43.5
Note. Еtot is the total energy (1 a.u. = 627.5095 kcal mol–1), ZPE is
the zeroꢀpoint energy, and ω is the lowest harmonic vibrational
1
frequency.

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
Ukhin et al.
Scheme 2
O
1.388
C
1.244
a
N
1.437
1.482
N
C1.396
C
C
1.406
1.460
C
1.396
C
1.395
1.384
1.543
1.419
C
C
C
1.483
C
C
N
1.420
1.388
1.403
1.390
C
1.025
1.419
C
1.408
C
1.385
1.475
1.792
C
O
1.242
4a
1.866
O
O
1.230
1.015
b
C 1.370
C
1.244
N
1.423
1.496
1.413
1.498
N
1.398
C
C
C
1.448
C
1.391
C 1.547
1.413
1.418
C
1.387
C
C
1.410
N
1.486
C
1.406
1.399
1.407
C
1.394
C
C
1.391
1.392
4b
O
c
1.388
C
1.241
N
O
1.239
1.494
1.434
1.388
1.497
C
C
1.405
N
C 1.403
C
C
1.410
C
C
1.460
1.398
1.403
1.387
C
1.399
1.419
C
C
C
1.486
1.527
C
C
N
1.403
1.400
Compound 7c was characterized by Xꢀray diffraction
1.412
C
(Fig. 3, Tables 2 and 3).
1.388
4c
C(18)
Fig. 2. Geometric characteristics of the most stable conformers 4a
(∆E = 0) (a), 4b (∆E = 12.25) (b), and 4c (∆E = 4.14) (c) calculated
at the B3LYP/3ꢀ21G* level of theory. The bond lengths are given
in Å.
C(17)
C(16)
N(3)
O(1)
second 1,5ꢀproton shift. These rearrangements proceed
very easily in structures analogous to 6.8
Compound 7a is readily alkylated at the N(6) atom
with haloalkyls at room temperature in DMSO or DMF in
the presence of NaOH or NaH (Scheme 2).
We failed to replace the H atom at N(6) under these
conditions in the reactions with tosyl and mesyl chlorides,
ethyl chloroacetate and bromoacetate, and phenacyl broꢀ
mide. In all cases, only the starting compound 7a was
isolated from the reaction mixture. Compound 7a does
not react with acetic anhydride even under reflux.
N(2)
C(3)
C(9)
C(10)
C(4)
C(8)
C(15)
C(5)
C(6)
C(11)
N(1)
C(1)
C(14)
C(13)
C(2)
C(7)
C(12)
Fig. 3. Molecular structure of compound 7c.

Benzo[1,2,4]triazepine[3,4ꢀa]isoindoleꢀ5ꢀone
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
189
Table 2. Selected bond lengths (d/Å) and bond angles (ω/deg) in
molecule 7c
Table 3. Selected torsion angles (ϕ/deg) in molecule 7c
Torsion angle
ϕ/deg
Parameter
Value
Parameter
Value
N(1)—C(11)—C(10)—C(9)
C(8)—N(1)—C(11)—C(10)
N(2)—C(8)—N(1)—C(11)
N(3)—N(2)—C(8)—N(1)
C(9)—N(3)—N(2)—C(8)
C(10)—C(9)—N(3)—N(2)
C(11)—C(10)—C(9)—N(3)
11.6(3)
31.4(3)
30.1(3)
–12.8(3)
26.5(3)
8.5(3)
Bond length
N(1)—C(1)
N(1)—C(8)
N(1)—C(11)
N(2)—N(3)
N(2)—C(8)
N(3)—C(9)
d/Å
Bond length
d/Å
1.485(2) O(1)—C(9)
1.399(2) C(9)—C(10)
1.410(2) C(10)—C(11)
1.397(2) C(1)—C(2)
1.284(2) C(2)—C(3)
1.358(2) C(3)—C(8)
1.230(2)
1.505(2)
1.408(2)
1.497(2)
1.386(2)
1.469(2)
–37.6(3)
Bond angle
ω/deg
Bond angle
ω/deg
129.8(1)
washed with hot PriOH and petroleum ether. A yellow crystalline
compound poorly soluble in most organic solvents was obtained;
m.p. 238—240 °C (from propylenecarbonate). The yield was 1.8 g
(36%). Positive ion mass spectrum: 249. Found (%): C, 72.16; H,
4.57; N, 17.30. C15H11N3O. Calculated (%): C, 72.28; H, 4.45; N,
16.86.
C(1)—N(1)—C(8) 110.6(1) N(2)—N(3)—C(9)
C(1)—N(1)—C(11) 120.3(1) C(16)—N(3)—C(9) 119.6(1)
C(8)—N(1)—C(11) 123.6(1) N(3)—C(9)—C(10) 121.6(1)
N(1)—C(8)—N(2) 133.2(1) C(9)—C(10)—C(11) 127.1(1)
C(8)—N(2)—N(3) 123.8(1) C(10)—C(11)—N(1) 122.2(1)
N(2)—N(3)—C(16) 110.6(1)
12HꢀBenzo[5,6]ꢀ6ꢀmethyl[1,2,4]triazepino[3,4ꢀa]isoinꢀ
dolꢀ5ꢀone (7b). A suspension of NaH (0.14 g, 3.5 mmol) was
dissolved in DMSO (6 mL), heterocycle 7a (0.75 g, 3 mmol) was
added, and the reaction mixture was triturated. The precipitate was
dissolved, after which the reaction mixture solidified. Then MeI
(0.5 mL, 8 mmol) was added, the mixture was triturated with a rod
for 5 min, and MeOH (10 mL) was added. The precipitate was
filtered off and recrystallized successively from PriOH (75 mL) and
CCl4 (50 mL). A yellow crystalline compound was obtained, m.p.
157—159 °C. The yield was 0.4 g (75%). Found (%): C, 73.28; H,
4.77; N, 15.82. C16H13N3O. Calculated (%): C, 72.99; H, 4.98;
N, 15.96.
12HꢀBenzo[5,6]ꢀ6ꢀisopropylꢀ1,2,4]triazepino[3,4ꢀa]isoꢀ
indolꢀ5ꢀone (7c). A suspension of NaH (0.1 g, 2.5 mmol) was
added portionwise to a suspension of heterocycle 7a (0.5 g, 2 mmol)
in DMSO (5 mL), the reaction mixture being triturated with a rod.
Then PriI (0.3 mL, 3 mmol) was added to the solidified mixture, and
the mixture was triturated with a rod. The mixture liquefied and
warmed up and then again solidified. The precipitate was filtered off
and washed with H2O. A yellow compound was obtained in a yield
of 0.3 g. An additional amount of the yellow compound (0.24 g) was
precipitated from the filtrate with a 1 : 1 MeOH—H2O mixture.
The precipitates were combined and recrystallized from isooctane
(20 mL). A yellow crystalline compound was obtained, m.p.
119—125 °C. The yield was 0.39 g (67%). The structure was estabꢀ
lished by Xꢀray diffraction.
Molecule 7c consists of four fused cyclic fragments.
Two benzene rings at the periphery of the molecule are
planar, and the dihedral angle between these rings is 29.3°.
The fiveꢀmembered ring fused to the benzene ring
C(2)...C(7) is also planar and is coplanar with the benzene
ring. The central sevenꢀmembered nitrogenꢀcontaining
heterocycle adopts a twist conformation; the correspondꢀ
ing torsion angles are listed in Table 3.
The N(1) and N(3) atoms have a planarꢀtrigonal conꢀ
figuration. The sums of the bond angles at these atoms are
354.5(3) and 360.0(3)°, respectively. The lengths of the double
(N(2)—C(8)) and single (N(2)—N(3)) bonds (1.284(2)
and 1.397(2) Å, respectively) are indicative of a substantial
localization of the πꢀelectron density on the double bond.
The alkylation of compound 7a at the oxygen atom is
principally possible. However, the presence of carbonyl
stretching bands in the spectra of compounds 7b—k (Table
4) confirms that all these compounds are alkylation prodꢀ
ucts at the nitrogen atom.
Experimental
12HꢀBenzo[5,6]ꢀ6ꢀallyl[1,2,4]triazepino[3,4ꢀa]isoindolꢀ
5ꢀone (7d). Heterocycle 7a (0.75 g, 3 mmol) was added to a suspenꢀ
sion of NaH (0.14 g, 3.5 mmol) dissolved in DMSO (6 mL), and
the reaction mixture was triturated with a rod. The reaction mixture
rapidly solidified. Allyl bromide (0.5 mL, 5.7 mmol) was added,
and the mixture was triturated until a new precipitate formed. Then
50% MeOH (10 mL) was added, and the precipitate was filtered off,
washed with 50% MeOH, and recrystallized from CCl4 (10 mL).
A yellow compound was obtained, m.p. 102—109 °C, in nearly
quantitative yield. Found (%): C, 74.51; H, 5.60; N, 14.35.
C18H15N3O. Calculated (%): C, 74.72; H, 5.23; N, 14.52.
12HꢀBenzo[5,6]ꢀ6ꢀpropargyl[1,2,4]triazepino[3,4ꢀa]isoꢀ
indolꢀ5ꢀone (7e). Sodium hydroxide (0.5 g, 1.25 mmol) was trituꢀ
rated under a layer of DMSO (2.5 mL), heterocycle 7a (0.17 g,
0.7 mmol) was added, and the reaction mixture was triturated with
a rod for 10 min. Then a toluene solution of propargyl bromide
The IR spectra were recorded on a Specord IRꢀ75 instrument in
Nujol mulls. The H NMR spectra were measured on a Varian
1
UNITYꢀ300 spectrometer. The mass spectra were obtained on a
Finnigan MAT INCOS 50 LCꢀmass spectrometer using a direct
inlet probe. The spectroscopic characteristics of the reaction prodꢀ
ucts are given in Table 4. A 57—63% NaH suspension in a mineral
oil (Lancaster) and a 80% toluene solution of propargyl bromide
(Acros) were used.
12HꢀBenzo[5,6][1,2,4]triazepino[3,4ꢀa]isoindolꢀ5(6H)ꢀ
one (7a). A hot solution of aldehyde 2 (2.7 g, 20 mmol) in PriOH
(10 mL) was added to a hot solution of hydrazide 1 (3 g, 20 mmol) in
PriOH (15 mL). The mildly exothermic reaction was observed,
which was accompanied by the color intensification and the forꢀ
mation of a crystalline precipitate in due course. The reaction mixꢀ
ture was refluxed for 15 min. The hot precipitate was filtered off and

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Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
Ukhin et al.
Table 4. IR spectra (Nujol mulls) and 1H NMR spectra
Compoꢀ
und
IR,
ν/cm–1
Solvent
1H NMR
(δ, (J/Hz))
7a
7b
7c
3260, 3127 (NH), 1687,
1640 (CO), 1594, 1487,
1475 (arom.)
1687, 1640 (C=O), 1621,
1594, 1567, 1494 (ароm)
DMSOꢀd6
4.85 (s, 2 H, CH2); 6.85 (m, 2 H, SНarom); 7.30—7.50 (m, 4 H,
SНarom); 7.55 (br.d, 1 H, SНarom); 7.96 (dd, 1 H, S(10)Н,
3J = 7.5, 4J = 1.0); 9.68 (s, 1 H, NH)
3.43 (s, 3 H, CH3); 4.83 (s, 2 H, CH2); 6.77 (d, 1 H, SНarom, J = 8.3);
6.95 (m, 1 H, SНarom); 7.20—7.60 (m, 5 H, SНarom); 7.72 (d, 1 H,
SНarom, J = 7.5); 8.11 (dd, 1 H, S(10)Н, 3J = 7.9, 4J = 1.75)
1.30 (d, 6 H, 2 SН3, J = 6.6); 4.82 (s, 2 H, CH2); 5.04 (quint, 1 H,
CDCl3
CDCl3
1687, 1669 (CO), 1614,
1594, 1567, 1487 (arom.)
SН, J = 6.6); 6.75 (d, 1 H, SНarom, J = 8.2); 6.94 (t, 1 H, SНarom
,
J = 7.5); 7.20—7.60 (m, 4 H, SНarom); 7.76 (d, 1 H, SНarom, J = 7.5);
8.12 (dd, 1 H, S(10)Н, 3J = 7.9, 4J = 1.75)
7d
7e
1680 (CO), 1614, 1587,
1567, 1487 (arom.)
CDCl3
CDCl3
4.43 (m, 2 H, SН2); 4.82 (s, 2 H, S(5)Н2); 5.10—5.50 (m, 2 H, =SН2);
6.03 (m, 1 H, SН=); 6.77 (d, 1 H, SНarom, J = 8.2); 6.95 (m, 1 H,
SНarom); 7.20—7.60 (m, 4 H, SНarom); 7.71 (d, 1 H, SНarom, J = 7.4);
8.13 (dd, 1 H, S(10)Н, 3J = 7.9, 4J = 1.7)
2.26 (t, 1 H, ≡SН, J = 2.4); 4.56 (d, 2 H, SН2, J = 2.4); 4.82 (s, 2 H,
S(5)Н2); 6.77 (d, 1 H, SНarom, J = 8.3); 6.95 (m, 1 H, SНarom);
7.30—7.55 (m, 4 H, SНarom); 7.77 (d, 1 H, SНarom, J = 7.4); 8.17
(dd,1 H, S(10)H, 3J = 7.9, 4J = 1.8)
3253 (≡CH); 2167 (C≡C),
1680 (CO), 1621, 1594,
1487 (arom.)
7f
7g
7h
7i
1674 (CO), 1607, 1580,
1555, 1487 (arom.)
CDCl3
CDCl3
4.79 (s, 2 H, S(5)Н2); 5.01 (s, 2 H, SН2); 6.74 (d, 1 H, SНarom,
J = 8.3); 6.94 (m, 1 H, SНarom); 7.10—7.60 (m, 11 H, SНarom); 7.96
(d, 1 H, SНarom, J = 7.4); 8.13 (dd, 1 H, S(10)Н, 3J = 7.9, 4J = 1.7)
1687, 1634 (CO), 1614,
1587, 1560, 1487 (arom.)
4.84 (s, 2 H, S(5)Н2); 5.16 (s, 2 H, SН2); 6.79 (d, 1 H, SНarom,
J = 8.0); 6.96 (m, 1 H, SНarom); 7.10—7.55 (m, 8 H, SНarom); 7.63
(d, 1 H, SНarom, J = 7.9); 8.16 (dd, 1 H, S(10)Н, 3J = 7.9, 4J = 1.6)
4.85 (s, 2 H, S(5)Н2); 4.90 (s, 2 H, SН2); 6.80—7.00 (m, 2 H, SНarom);
7.20—7.50 (m, 8 H, SНarom); 7.58 (d, 1 H, SНarom, J = 7.7); 7.95
(br. dd, 1 H, S(10)Н)
1687, 1640 (CO), 1620,
1594, 1567, 1487 (arom.)
DMSOꢀd6
DMSOꢀd6
DMSOꢀd6
1687 (CO); 1620, 1594,
1587, 1567, 1514, 1487
(arom.), 1247, 1228 (S—О)
1687, 1640 (CO),
1620, 1594, 1567, 1487
(arom.)
3.73 (s, 3 H, SН3); 4.80, 4.88 (both s, 2 H each, SН2); 6.78 (d, 2 H,
SНarom, J = 8.6); 6.90 (m, 2 H, SНarom); 7.20—7.55 (m, 6 H, SНarom);
7.61 (d, 1 H, S(7)Н, J = 7.6); 7.94 (dd, 1 H, S(10)Н, 3J = 7.9, 4J = 1.6)
4.89, 4.90 (both s, 2 H each, SН2); 6.90 (m, 2 H, SНarom); 7.20—7.50
(m, 6 H, SНarom); 7.61 (d, 1 H, SНarom, J = 7.6); 7.8 (m, 1 H,SНarom);
7j
7.97 (dd, 1 H, S(10)Н, 3J = 7.8, 4J = 1.6); 8.40 (d, 1 H,SНarom
J = 4.5); 8.60 (c, 1 H, SНarom
,
)
7k
1674 (CO), 1634, 1607,
1594, 1587, 1554, 1487
(arom.)
DMSOꢀd6
4.89, 4.92 (both s, 2 H each, SН2); 6.70—7.10 (m, 2 H, SНarom);
7.20—7.70 (m, 7 H, SНarom); 7.95 (d, 1 H, SНarom, J = 7.9); 8.43
(d, 2 H, SНarom, J = 5.8)
(0.12 mL, ∼1 mmol) was added, the reaction mixture was triturated
and kept for 30 min, H2O (5 mL) was added, and the precipitate was
filtered off, washed with H2O and MeOH, and recrystallized from
CH3CN (12 mL). A yellow compound was obtained, m.p. 183—
184 °C. The yield was 0.1 g (50%). Found (%): C, 74.87; H, 4.89; N,
14.36. C18H13N3O. Calculated (%): C, 75.25; H, 4.56; N, 14.62.
12HꢀBenzo[5,6]ꢀ6ꢀbenzyl[1,2,4]triazepino[3,4ꢀa]isoinꢀ
dolꢀ5ꢀone (7f). Sodium hydroxide (0.16 g, 4 mmol) was triturated
in DMSO (3 mL), heterocycle 7a (0.5 g, 2 mmol) was added, the
reaction mixture was triturated for 5 min, and benzyl chloride
(0.3 mL, 2.6 mmol) was added with stirring. After 30 min, 50%
MeOH (12 mL) was added, and the precipitate (0.6 g) was filtered
off and recrystallized from MeCN (15 mL). Yellow crystals were
obtained, m.p. 142—143 °C. The yield was 0.42 g (62%). Found
(%): C, 77.52; H, 5.34; N, 12.18. C22H17N3O. Calculated (%): C,
77.86; H, 5.05; N, 12.38.
12HꢀBenzo[5,6]ꢀ6ꢀ(2ꢀchlorobenzyl)[1,2,4]triazepino[3,4ꢀ
a]isoindolꢀ5ꢀone (7g). Sodium hydroxide (0.16 g, 4 mmol) was
triturated in DMSO (3 mL), heterocycle 7a (0.5 g, 2 mmol) was
added, and the reaction mixture was triturated for 10 min. Then
oꢀchlorobenzyl chloride (0.4 mL, 3 mmol) was added, the reaction
mixture was kept for 1 h, and MeOH (5 mL) was added. The
precipitate was filtered off (0.7 g) and recrystallized from ethyl acꢀ
etate (110 mL). A yellow compound was obtained, m.p.
203—205 °C. The yield was 0.49 g (65%). Found (%): C, 70.45; H,
4.63; N, 10.95. C22H16N3OCl. Calculated (%): C, 70.68; H, 4.31;
N, 11.24.
12HꢀBenzo[5,6]ꢀ6ꢀ(4ꢀchlorobenzyl)[1,2,4]triazepino[3,4ꢀ
a]isoindolꢀ5ꢀone (7h). Sodium hydroxide (0.1 g, 2.5 mmol) was
triturated in DMF (3 mL), heterocycle 7a (0.25 g, 1 mmol) was
added, the reaction mixture was triturated until solidification took
place (∼5 min), and a solution of pꢀchlorobenzyl chloride (0.28 g,

Benzo[1,2,4]triazepine[3,4ꢀa]isoindoleꢀ5ꢀone
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
191
Table 5. Crystal parameters and the Xꢀray diffraction data collecꢀ
tion and refinement statistics
12HꢀBenzo[5,6]ꢀ6ꢀ(3ꢀpicolyl)[1,2,4]triazepino[3,4ꢀa]isoꢀ
indolꢀ5ꢀone (7j). Sodium hydroxide (0.1 g, 2.5 mmol) was trituꢀ
rated in DMF (2 mL), heterocycle 7a (0.25 g, 1 mmol) was added,
and the reaction mixture was triturated for 5 min. A freshly preꢀ
pared solution of 3ꢀpicolyl chloride hydrochloride (0.2 g, 1.2 mmol)
in a mixture of DMF (3 mL) and pyridine (0.2 mL) was added to the
solidified mixture, and the resulting mixture was slightly warmed
(30—40 °C) and kept for 1 h. Then 50% MeOH (10 mL) was added,
the mixture was cooled on ice, and the precipitate was filtered off,
washed with H2O and 50% EtOH, and recrystallized from PriOH
(50 mL). A yellow compound was obtained, m.p. 183—186 °C. The
yield was 0.2 g (59%). Found (%): C, 74.32; H, 4.89; N, 16.20.
C21H16N4O. Calculated (%): C, 74.10; H, 4.74; N, 16.46.
12HꢀBenzo[5,6]ꢀ6ꢀ(4ꢀpicolyl)[1,2,4]triazepino[3,4ꢀa]isoꢀ
indolꢀ5ꢀone (7k). Compound 7k was synthesized analogously to 7j
by the addition of 4ꢀpicolyl chloride hydrochloride (0.25 g,
1.5 mmol) and recrystallized from PriOH (10 mL). A yellow comꢀ
pound was obtained, m.p. 164—167 °C. The yield was 0.13 g (38%).
Found (%): C, 74.43; H, 4.95; N, 16.58. C21H16N4O. Calculated
(%): C, 74.10; H, 4.74; N, 16.46.
Xꢀray diffraction study. A single crystal of compound 7c coated
with perfluorinated oil was mounted on a Bruker SMARTꢀCCD
diffractometer under a cold nitrogen stream. The experimental
Xꢀray data were collected from a single crystal using the ωꢀscanꢀ
ning technique and MoꢀKα radiation. The crystallographic paramꢀ
eters and the Xꢀray diffraction data collection and refinement staꢀ
tistics are given in Table 5.The experimental reflections were processed
with the use of the Bruker SAINT software.9 The structure was solved
by direct methods and refined by the fullꢀmatrix leastꢀsquares
method based on F2 with anisotropic displacement parameters for
all nonhydrogen atoms. The hydrogen atoms were located in differꢀ
ence Fourier maps and refined isotropically. All calculations were
carried out using the SHELXTLꢀPlus program package.10
The atomic coordinates and other experimental data were deposited
with the Cambridge Structural Database.*
Parameter
Value
Molecular formula
Molecular weight/kg kmol–1
Crystal system
Space group
C18H17N3O
291.35
Orthorhombic
Р212121
а/Å
8.6041(4)
10.6309(6)
15.9100(8)
1455.3(1)
4
b/Å
с/Å
V
Z
ρ
/Å3
calc/g cm–3
0.085
F(000)
616
0.302
0.34×0.26×0.14
120.0(2)
MoꢀKa (0.71073)
w
µ(MoꢀKα)/mm–1
Crystal dimensions/mm
Т/К
Radiation (λ/Å)
Scan mode
θꢀScanning range/deg
Ranges of reflection indices
2.30—28.99
–11 ≤ h ≤ 11,
–12 ≤ k ≤ 14,
–21 ≤ l ≤ 21
7920
Number of measured reflections
Number of independent reflections
3782
Rint
0.0192
Number of reflections with I > 2σ(I)
3782
Number of refinement variables
267
R Factors
based on reflections with I > 2σ(I)
R1
wR2
0.0351
0.0901
based on all reflections
R1
wR2
0.0422
0.0948
1.056
References
Goodnessꢀofꢀfit on F2
Residual electron density/e Å3, min/max
–0.191/0.266
1. M. Ghelardoni, V. Pestellini, Ann. Chimica (Roma), 1974, 64,
445.
2. V. Pestellini, M. Ghelardoni, G. Volterra, P. Del Soldato,
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4. M. Razvi, T. Ramalihgam, P.B. Sattur, Indian J. Chem., 1990,
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1.7 mmol) in DMF (2 mL) was added. Then the reaction mixture
was slightly warmed (30—40 °C) and allowed to stand for 2.5 h. The
precipitate was filtered off, twice washed with 50% MeOH, and
dried. An orange compound was obtained, m.p. 198—202 °C (from
MeCN). The yield was 0.29 g (77%). Found (%): C, 70.87; H, 4.42;
N, 11.13. C22H16N3OCl. Calculated (%): C, 70.68; H, 4.31;
N, 11.24.
5. Thode, J. Prakt. Chem., 1904, 69, 92.
6. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomꢀ
ery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M.
Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas,
J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci,
C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson,
P. Y. Ayala, Q. Cui, K. Morokuma, D. K. Malick, A. D.
Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V.
12HꢀBenzo[5,6]ꢀ6ꢀ(4ꢀmethoxybenzyl)[1,2,4]triazepiꢀ
no[3,4ꢀa]isoindolꢀ5ꢀone (7i). Sodium hydroxide (0.1 g, 2.5 mmol)
was triturated in DMSO (2 mL), heterocycle 7a (0.25 g, 1 mmol)
was added, and the reaction mixture was triturated for 10 min.
4ꢀMethoxybenzyl chloride (0.17 mL, 1.2 mmol) was added to the
redꢀbrown precipitate. The reaction mixture was triturated and kept
for 50 min. Then 50% MeOH (5 mL) was added, and the orange
precipitate was filtered off, washed with 50% MeOH, and dried.
The product (0.32 g) was recrystallized from MeCN (7 mL), washed
with EtOH, and dried. A yellow compound was obtained, m.p.
150—153 °C. The yield was 0.25 g (68%). Found (%): C, 74.48; H,
5.34; N, 11.30. C23H19N3O2. Calculated (%): C, 74.78; H, 5.18;
N, 11.37.
* These data can be obtained, free of charge, on application to the
Cambridge Crystallographic Data Centre: CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: (+44) 1223 336 033; eꢀmail:
deposit@ccdc.cam.ac.uk), refcode 675784.

192
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Received April 23, 2007;
in revised form November 13, 2007