Synthesis of novel dibenzo-2,6,9-triazabicyclo[3.3.1]nonanes from o-tosylamino- and o-mesylaminobenzaldehydes

Article abstract of DOI:10.1007/s11172-005-0111-0

Condensation of o-tosylaminobenzaldehyde with γ-aminobutyric, 4-aminophenylthioacetic, and p-aminobenzoic acids and β-alanine gave 6,12-epimino-5,11-ditosyl-5,6,11,12-tetrahydrodibenzo[b, f]-1,5-diazocines with carboxyl-containing substituents at the brid

Full text of DOI:10.1007/s11172-005-0111-0

2262
Russian Chemical Bulletin, International Edition, Vol. 53, No. 10, pp. 2262—2268, October, 2004
✾
Synthesis of novel dibenzoꢀ2,6,9ꢀtriazabicyclo[3.3.1]nonanes
from oꢀtosylaminoꢀ and oꢀmesylaminobenzaldehydes
b
L. Yu. Ukhina and L. G. Kuz´mina
ꢀ
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 (095) 953 1279. Eꢀmail: kuszmina@igic.ras.ru
Condensation of oꢀtosylaminobenzaldehyde with γꢀaminobutyric, 4ꢀaminophenylthioacetic,
and pꢀaminobenzoic acids and βꢀalanine gave 6,12ꢀepiminoꢀ5,11ꢀditosylꢀ5,6,11,12ꢀtetraꢀ
hydrodibenzo[b, f ]ꢀ1,5ꢀdiazocines with carboxylꢀcontaining substituents at the bridging
N atoms. The structures of three products were examined by Xꢀray diffraction analysis. Conꢀ
densation of oꢀmesylaminobenzaldehyde (prepared by the McFadyen—Stevens reaction) with
NH4OAc and primary amines afforded 6,12ꢀepiminoꢀ5,11ꢀdimesylꢀ5,6,11,12ꢀtetrahydrodiꢀ
benzo[b, f ]ꢀ1,5ꢀdiazocine derivatives.
Key words: oꢀtosylaminobenzaldehyde, amino acids, 6,12ꢀepiminoꢀ5,11ꢀditosylꢀ5,6,11,12ꢀ
tetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine derivatives, oꢀmesylaminobenzaldehyde, ammonium acꢀ
etate, primary amines, 6,12ꢀepiminoꢀ5,11ꢀdimesylꢀ5,6,11,12ꢀtetrahydrodibenzo[b, f ]ꢀ1,5ꢀ
diazocine derivatives, Xꢀray diffraction analysis.
Earlier,1 we synthesized dibenzoꢀ2,6,9ꢀtriazabiꢀ
cyclo[3.3.1]nonanes from oꢀtosylaminobenzaldehyde and
primary amines. Some of these compounds contained
pharmacophoric phenylsulfonylamino groups at the bridgꢀ
ing N atoms.2 It was of interest to carry out such condenꢀ
sation reactions with biologically active amino acids. Inꢀ
corporation of the N atom of their amino groups into
bicyclic structures of the target products could change
their properties and impart new kinds of biological acꢀ
tivities.
Scheme 1
Condensation of oꢀtosylaminobenzaldehyde 1 with
γꢀaminobutyric (2a) and pꢀaminophenylthioacetic
acids (2b), βꢀalanine (2c), and 4ꢀaminobenzoic acid (2d)
gave 6,12ꢀepiminotetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocines
3a—d with carboxylꢀcontaining substituents at position 13
(Scheme 1).
Their structures were established by Xꢀray diffraction
analysis (see below) and confirmed by IR and NMR specꢀ
tra (Table 1).
Reactions of αꢀamino acids with aldehyde 1 yield no
carboxylꢀcontaining diazocines.
To define the scope of this reaction, we studied the
behavior of oꢀmesylaminobenzaldehyde synthesized by
the McFadyen—Stevens reaction as described for oꢀtosylꢀ
aminobenzaldehyde (1)3,4 (Scheme 2).
It turned out that aldehyde 6 reacted with ammonium
acetate and primary amines to give 6,12ꢀepiminoꢀ5,11ꢀ
dimesylꢀ5,6,11,12ꢀtetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine
derivatives 7a—e; however, the yields of the products were
lower than the yields of their tosyl analogs1 (Scheme 3).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2165—2171, October, 2004.
1066ꢀ5285/04/5310ꢀ2262 © 2004 Springer Science+Business Media, Inc.

NꢀTosyl(mesyl)dibenzoꢀ1,5ꢀdiazocines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
2263
Table 1. IR and 1H NMR spectroscopic data for compounds 3a—d
Comꢀ
pound
IR,
ν/cm–1
1H NMR (DMSOꢀd6),
δ (J/Hz)
3a
1727, 1714 (CO),
1607, 1581,
1487 (arom.),
1334, 1160 (SO2)
1714, 1694 (CO),
1594, 1581, 1487,
1480 (arom.),
1341, 1154 (SO2)
1727, 1714 (CO),
1607, 1581,
1.47, 1.63 (both m, 1 H each, СН2); 1.94, 2.21 (both m, 2 H each, СН2); 2.39 (s, 6 H, 2 Me);
6.03 (s, 2 H, 2 СН); 7.05—7.25 (two br.t, 4 H, С(2)Н, С(3)Н, С(8)Н, С(9)Н); 7.29 (d,
4 H, 2 С(3´)Н, 2 С(5´)Н, J = 8.2); 7.39 (br.d, 2 H, С(1)Н, С(7)Н); 7.58 (d, 2 H,
С(4)Н, С(9)Н, J = 8.3); 7.63 (d, 4 H, 2 С(2´)Н, 2 С(6´)Н, J = 8.2)
3b*
3с
2.27 (s, 6 H, 2 Me); 3.65 (s, 2 H, SCH2); 6.39 (d, 2 H, С(2″)Н, C(6″)H, J = 8.6);
6.73 (s, 2 H, 2 СН); 6.86 (d, 4 H, 2 С(3´)Н, 2 С(5´)Н, J = 8.2); 7.02 (d, 4 H, 2 С(2´)H,
2 C(6´)H, J = 8.2); 7.10—7.22 (m, 6 H, СН (arom.)); 7.54 (dd, 2 H, С(1)Н, С(7)Н,
4
3J = 7.5, J = 1.6); 7.64 (br.d, 2 H, С(4)Н, С(10)Н)
2.10 (m, 1 H, СН2); 2.30—2.50 (m, 9 H, 2 Me, СН2, 1 Н from СН2); 6.08 (s, 2 H, 2 СН);
7.00—7.25 (two br.t, 4 H, С(2)Н, С(3)Н, С(8)Н, С(9)Н); 7.28 (d, 4 H, 2С(3´)Н,
2 С(5´)Н, J = 8.2); 7.38 (br.d, 2 H, С(1)Н, С(7)Н); 7.53 (d, 2 H, С(4)Н, С(9)Н,
J = 8.2); 7.66 (d, 4 H, 2 С(2´)Н, 2 С(6´)Н, J = 8.2); 12.17 (s, 1 H, ОН)
2.26 (s, 6 H, 2 Me); 6.54 (d, 2 H, С(2″)Н, C(6″)H, J = 8.6); 6.83 (s, 2 H, 2 СН);
6.85 (br.d, 4 H, 2 С(3´)Н, 2 С(5´)Н); 6.98 (d, 4 H, 2 С(2´)H, 2 C(6´)H, J = 8.2);
7.15—7.35 (m, 4 H, СН (arom.)); 7.53 (br.d, 2 H, СН (arom.)); 7.65 (d, 2 H, СН (arom.),
J = 8.0); 7.71 (d, 2 H, C(3″)H, C(5″)H, J = 8.6)
1487 (arom.),
1341, 1161 (SO2)
1694 (СО), 1607,
1581, 1514,
1487 (arom.), 1354,
1347, 1174, 1161 (SO2)
3d
* In CDCl3.
Scheme 2
in the reaction with compound 6. The lowest yields were
obtained in the reactions with aromatic amines, which are
less basic than aliphatic amines by on average six orders of
magnitude. However, the possibility of condensation
seems to be determined by additional factors that are
unclear. For instance, 4ꢀfluoroaniline does not react with
aldehyde 6, although its basicity (pKa = 4.54) is very close
to that of aniline (pKa = 4.60).5
The crystal structures of compounds 3a—c were estabꢀ
lished by Xꢀray diffraction analysis (Figs 1—3; Tables 3, 4).
Both heterocycles in the bicycles exist in the sofa
conformation. The angle C(1)N(3)C(8) goes out of
the planes of the fiveꢀmembered fragments including
the N(1) or N(2) atom (C(1)N(1)C(10)C(9)C(8) or
C(1)C(2)C(3)N(2)C(8)). The corresponding dihedral
angles noticeably differ both for the two rings in the same
molecule and for different molecules, varying from 48°
to 72° (see Table 3). At the same time, the dihedral angle
between the planes of the benzene rings in the phenylꢀ
sulfonyl substituents, which seems to depend mainly on
the packing effects in the crystal, shows a comparatively
small scatter over compounds 3a—c (from 98.4° to 104.0°).
In all the three structures, the central N(3) atom of
the bicyclic system has a pyramidal bond configuraꢀ
tion. The sum of the bond angles at the N(3) atom is
339.7° in 3a, 347.7° in 3b, and 334.7° in 3c. The bond
configurations of the N(1) and N(2) atoms are signifiꢀ
cantly more flattened. The sum of the bond angles at
these atoms is 355.7° and 359.9° in compound 3a and
Scheme 3
R = Me (b), Et (c), Ph (d), 4ꢀMeC6H4 (e)
i. ∆, PrOH; ii. ∆, PrOH or AcOH.
The IR and NMR spectroscopic data for compounds
5—7 are given in Table 2.
As with oꢀtosylaminobenzaldehyde (1), we revealed a
correlation between the basicity and reactivity of an amine
360.0° and 358.0° in compound 3c. The geometry of comꢀ
pound 3b is slightly different. The sum of the bond angles
at the N(1) atom is 357.5°, which corresponds to a virtuꢀ
ally planar bond configuration (as in compounds 3a

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
Ukhin and Kuz´mina
Table 2. IR and 1H NMR spectroscopic data for compounds 5, 6, and 7a—e
Comꢀ
pound
IR,
ν/cm–1
1H NMR (CDCl3),
δ (J/Hz)
5*
3353, 3207 (NH), 1647 (CO),
1607, 1587, 1534, 1501 (arom.),
1341, 1327, 1167, 1154 (SO2)
3147 (NH), 1674 (CO), 1607,
1581, 1487 (arom.), 1327, 1147 (SO2)
3353 (NH), 1600, 1575, 1487 (arom.),
1354, 1341, 1327, 1167, 1161,
1154 (SO2)
3.01, 3.04 (both s, 3 H each, Me); 7.17 (m, 1 H, СН (arom.)); 7.54 (m, 2 H,
СН (arom.)); 7.85 (d, 1 H, С(6)Н, J = 7.5); 9.60 (d, 1 H, NH, J = 2.5);
10.40 (s, 1 H, NH); 10.96 (d, 1 H, NH, J = 2.5)
3.12 (s, 3 H, Me); 7.28 (m, 1 H, СН (arom.)); 7.60—7.80 (m, 3 H,
СН (arom.)); 9.93 (s, 1 H, СНО); 10.62 (s, 1 H, NH)
3.04 (s, 6 H, 2 Me); 4.50 (t, 1 H, NH, J = 3.0), 6.22 (d, 2 H, 2 СН,
J = 3.0); 7.05—7.30 (m, 4 H, СН (arom.)); 7.89 (dd, 2 H, C(1)H, С(7)Н,
3J = 7.5, 4J = 1.5); 7.54 (d, 2 H, C(4)H, C(10)H, J = 8.1)
6
7a*
7b
7с
7d
7е
1607, 1587, 1581, 1487 (arom.),
1354, 1341, 1327, 1154 (SO2)
2.52 (s, 3 H, NMe); 3.05 (s, 6 H, 2 Me), 6.04 (s, 2 H, 2 СН);
7.05—7.30 (m, 4 H, СН (arom.)); 7.44 (dd, 2 H, С(1)Н, С(7)Н, J = 7.6,
4J = 1.6); 7.54 (dd, 2 H, С(4)Н, С(10)Н, 3J = 8.35, 4J = 0.8)
3
1607, 1581, 1487 (arom.),
1341, 1321, 1161, 1141 (SO2)
1.28 (t, 3 H, Me, J = 7.2); 2.58, 2.73 (both m, 1 H each, СН2); 3.04 (s, 6 H,
2 Me), 6.16 (s, 2 H, 2 СН); 7.05—7.30 (m, 4 H, СН (arom.)); 7.46 (dd, 2 H,
3
С(1)Н, С(7)Н, J = 7.6, 4J = 1.6); 7.55 (d, 2 H, С(4)Н, С(10)Н, J = 8.3)
1607, 1587, 1501, 1487 (arom.),
1354, 1334, 1167, 1154 (SO2)
2.48 (s, 6 H, 2 Me), 6.94 (s, 2 H, 2 СН), 6.97—7.40 (m, 9 H, СН (arom.));
4
7.59 (dd, 2 H, С(1)Н, С(7)Н, 3J = 7.5, J = 1.8); 7.68 (d, 2 H, С(4)Н,
С(10)Н, J = 8.0)
1607, 1600, 1587, 1514, 1487 (arom.),
1347, 1327, 1167, 1154 (SO2)
2.26 (s, 3 H, Me); 2.48 (s, 6 H, 2 Me), 6.88 (m, 4 H, 2 СН, 2 СН (arom.));
7.00—7.30 (m, 6 H, СН (arom.)); 7.58 (dd, 2 H, С(1)Н, С(7)Н, J = 7.5,
4J = 1.8); 7.68 (dd, 2 H, С(4)Н, С(10)Н, 3J = 8.3, 4J = 1.2)
3
* In DMSOꢀd6.
and 3c); the analogous sum of the bond angles at the N(2)
atom (349.3°) suggests a noticeable pyramidal character
of its bond configuration.
Hence, the geometry of the bicyclic framework in comꢀ
pounds 3a—c is not rigid as regards both the bond conꢀ
figurations of the N atoms and the dihedral angles in the
sixꢀmembered heterocycles.
Compounds 3a,b form centrosymmetrical dimers typiꢀ
cal of carboxylic acids through pairs of hydrogen bonds
(Figs 4, 5). These hydrogen bonds in structure 3a have the
O(6)
O(5)
C(32)
C(31)
C(21)
C(19)
C(30)
C(28)
C(26)
C(18)
C(17)
C(20)
C(29)
C(27)
C(25)
N(3)
C(24)
O(2)
C(16)
C(22)
C(2)
C(15)
C(1)
N(1)
O(4)
C(8)
S(1)
C(23)
N(2)
C(9)
S(2)
C(10)
C(3)
C(4)
O(1)
C(7)
C(11)
O(3)
C(14)
C(13)
C(6)
C(5)
C(12)
Fig. 1. Structure 3a.

NꢀTosyl(mesyl)dibenzoꢀ1,5ꢀdiazocines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
2265
O(6)
C(36)
C(35)
O(5)
S(3)
C(32)
C(31)
C(28)
C(33)
C(30)
C(19)
C(21)
C(26)
C(34)
C(18)
C(17)
C(25)
C(24)
C(29)
N(3)
C(20)
C(27)
O(4)
C(15)
O(2)
C(22)
C(1)
C(9)
C(23)
C(8)
N(2)
C(16)
S(1)
S(2)
N(1)
C(10)
C(11)
C(2)
C(3)
O(3)
O(1)
C(7)
C(4)
C(14)
C(13)
C(6)
C(12)
C(5)
Fig. 2. Structure 3b.
C(2´)
C(1´)
O(3´)
C(4´)
C(3´)
H(6)
O(1´)
O(6)
C(31)
C(28)
C(26)
O(5)
C(21)
C(30)
C(29)
C(27)
C(19)
C(25)
C(24)
C(18)
C(17)
N(3)
C(20)
O(2)
O(4)
C(9)
C(8)
N(2)
C(23)
C(22)
S(2)
C(1)
N(1)
C(15)
S(1)
C(2)
C(14)
C(13)
C(16)
C(3)
C(4)
C(10)
C(11)
O(3)
O(1)
C(7)
C(12)
C(5)
C(6)
Fig. 3. Structure 3c with a solvate molecule of ethyl acetate.

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
Ukhin and Kuz´mina
Table 3. Geometrical parameters of the 2,6,9ꢀtriazabiꢀ
cyclo[3.3.1]nonane fragment in compounds 3a—c
Parameter
3a
3b
3c
Bond
d/Å
N(1)—C(1)
N(1)—C(10)
N(1)—S(1)
N(2)—C(3)
N(2)—C(8)
N(2)—S(2)
N(3)—C(1)
N(3)—C(8)
N(3)—C(29)
C(1)—C(2)
C(2)—C(3)
C(8)—C(9)
C(9)—C(10)
1.493(2)
1.435(2)
1.651(2)
1.423(2)
1.507(2)
1.649(2)
1.447(2)
1.435(2)
1.470(2)
1.509(2)
1.402(2)
1.515(2)
1.400(2)
1.495(3)
1.442(4)
1.661(2)
1.446(3)
1.476(4)
1.673(2)
1.451(3)
1.463(4)
1.426(3)
1.522(4)
1.406(4)
1.513(4)
1.402(4)
ω/deg
1.521(3)
1.435(3)
1.649(2)
1.433(3)
1.484(3)
1.664(2)
1.443(3)
1.459(3)
1.479(3)
1.516(3)
1.399(3)
1.521(3)
1.403(3)
Fig. 4. Centrosymmetrical dimer in the crystal of 3a.
Bond angle
A different system of weak interactions was detected
in structure 3c, in which hydrogen bonding involves a
solvate molecule of ethyl acetate rather than the carboxy
group of the neighboring molecule (see Fig. 3). In this
structure, the distances H(6)...O(1´) and O(6)...O(1´) are
1.86 and 2.748(3) Å. These values correspond to a very
weak hydrogen bond which can be identified only from
the regular mutual geometries of the corresponding
fragments (angle C(1´)—O(1´)...H(6) 122°, angle
O(6)—H(6)...O(1´) 164.2°).
C(1)—N(1)—S(1)
C(1)—N(1)—C(10)
S(1)—N(1)—C(10)
C(8)—N(2)—S(2)
C(8)—N(2)—C(3)
S(2)—N(2)—C(3)
С(1)—N(3)—C(8)
C(1)—N(3)—C(29)
C(8)—N(3)—C(29)
Dihedral angle
C(1),N(3),C(8)/
C(1),N(1),C(10),C(9),C(8)
C(1),N(3),C(8)/
C(1),C(2),C(3),N(2),C(8)
C(2),C(3),C(4),C(5),C(6),C(7)/
C(9),C(10),C(11),C(12),C(13),C(14)
117.8(1)
115.2(1)
122.7(1)
120.0(1)
116.2(1)
123.7(1)
108.4(1)
115.6(1)
115.7(1)
120.7(2)
113.6(2)
123.2(2)
118.8(2)
112.9(2)
117.6(2)
108.2(2)
118.4(2)
121.1(2)
ϕ/deg
120.7(2)
115.6(2)
123.7(2)
119.6(2)
115.2(2)
123.2(2)
107.7(2)
113.9(2)
113.1(2)
59.4
50.2
48.0
72.3
59.4
54.9
98.4
Experimental
104.0
102.0
IR spectra were recorded on a Specord IR75 instruꢀ
ment (Nujol). 1H NMR spectra were recorded on a Varian
UNITYꢀ300 spectrometer.
oꢀTosylaminobenzaldehyde (1) was prepared as described
earlier.3,4
following parameters: O(5)...H(6A) 1.77 Å, O(5)...O(6A)
2.656(2) Å, angle O(5)...H(6A)—O(6A) 170°, and angle
C(32)—O(5)...H(6A) 124°.
The parameters of the hydrogen bonds in structure 3b
(see Fig. 5) (1.65 Å, 2.231(3) Å, 170°, and 120.9°, respecꢀ
tively) suggest a stronger interaction associated with the
more pronounced electronꢀwithdrawing properties of the
substituent in the carboxyl fragment.
13ꢀ(3ꢀCarboxypropyl)ꢀ6,12ꢀepiminoꢀ5,11ꢀditosylꢀ5,6,11,12ꢀ
tetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (3a). A mixture of aldeꢀ
hyde 1 (1.37 g, 5 mmol) and γꢀaminobutyric acid (2a) (0.50 g,
5 mmol) in 10 mL of PrOH was refluxed for 5 h and cooled.
The precipitate that formed was filtered off, washed with
EtOH (3 mL), and dried in air to give colorless crystals, m.p.
224—225 °C (from ethyl acetate). The yield of compound 3a
Fig. 5. Centrosymmetrical dimer in the crystal of 3b.

NꢀTosyl(mesyl)dibenzoꢀ1,5ꢀdiazocines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
2267
Table 4. Crystallographic parameters and a summary of data collection for compounds 3a—c
Parameter
3a
3b
3c
Molecular formula
Molar mass/kg kmol–1
C32H31N3O6S2
617.72
C36H31N3O6S3
697.21
C35H34N6O8S2
692.79
Crystal system
Space group
a/Å
b/Å
c/Å
Triclinic
Triclinic
Tricl–inic
P1
–
–
P1
P1
10.1866(14)
11.2535(15)
14.743(2)
72.039(3)
74.762(3)
68.880(3)
1477.7(3)
2
12.1487(4)
12.5199(4)
13.0127(5)
70.247(2)
67.511(2)
70.045(2)
1669.18(10)
2
10.6092(4)
13.1826(5)
13.6775(5)
107.034(2)
103.4430(10)
107.373(2)
1634.73(11)
2
α/deg
β/deg
γ/deg
V/Å3
Z
ρ
calc/g cm–3
1.388
1.388
1.407
F(000)
648
728
722
µ(MoꢀKα)/mm–1
Crystal size/mm
Temperature/K
θ range/deg
0.231
0.274
0.221
0.34×0.26×0.18
120.0(2)
1.47—29.00
–13 ≤ h ≤ 12
–15≤ k ≤ 10
–20 ≤ l ≤ 18
11656
0.18×0.12×0.10
120.0(2)
1.74—29.00
–12 ≤ h ≤ 16
–17 ≤ k ≤ 16
–14 ≤ l ≤ 17
13218
0.18×0.10×0.08
120.0(2)
1.66—29.00
–14 ≤ h ≤ 13
–17 ≤ k ≤ 16
–18 ≤ l ≤ 18
10943
Ranges of h, k, l indices
Number of measured reflections
Number of independent reflections
Rint
7741
0.0205
8534
0.0570
8055
0.0370
Number of reflections with I > 2σ(I )
Number of refined parameters
7741
513
4164
557
5087
570
R factors with I > 2σ(I )
R1
wR2
0.0509
0.1317
0.0591
0.1109
0.0579
0.1311
R factors for all reflections
R1
wR2
GOOF on F 2
0.0677
0.1477
1.078
0.1470
0.1303
0.889
0.1062
0.1473
0.926
Residual electron
density (min/max)/e•Å–3
–0.397/1.079
–0.374/0.342
–0.338/0.579
was 0.60 g (39%). Found (%): C, 62.18; H, 4.99; N, 6.60;
S, 10.65. C32H31N3O6S2. Calculated (%): C, 62.22; H, 5.06;
N, 6.80; S, 10.38.
that formed was filtered off, washed with 50% EtOH (50 mL),
dried in air, and recrystallized from ethyl acetate to give a 1 : 1
solvate 3c•EtOAc. IR (solvate), ν/cm–1: 1687 (CO in COOH),
1740 (CO in EtOAc). Heating of the solvate to 100—120 °C
completely removed ethyl acetate to give a colorless substance,
m.p. 248—250 °C. The yield of compound 3c was 0.50 g (33%).
Found (%): C, 61.30; H, 5.22; N, 7.29; S, 10.24. C31H29N3O6S2.
Calculated (%): C, 61.68; H, 4.84; N, 6.96; S, 10.62.
13ꢀ(4ꢀCarboxyphenyl)ꢀ6,12ꢀepiminoꢀ5,11ꢀditosylꢀ5,6,11,12ꢀ
tetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (3d). A mixture of aldeꢀ
hyde 1 (1.12 g, 4 mmol) and pꢀaminobenzoic acid (2d) (0.40 g,
3 mmol) in 15 mL of AcOH was refluxed for 4 h and cooled,
while periodically scratching with a rod. The precipitate that
formed was filtered off, washed with AcOH and hexane, and
twice recrystallized from MeCN to give a colorless substance,
m.p. 300—305 °C. The yield of compound 3d was 0.42 g (31%).
Found (%): C, 64.36; H, 4.81; N, 6.39; S, 10.12. C35H29N3O6S2.
Calculated (%): C, 64.50; H, 4.49; N, 6.45; S, 9.84.
13ꢀ[4ꢀ(Carboxymethylthio)phenyl]ꢀ6,12ꢀepiminoꢀ5,11ꢀdiꢀ
tosylꢀ5,6,11,12ꢀtetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (3b).
A mixture of aldehyde 1 (0.55 g, 2 mmol) and 4ꢀaminoꢀ
phenylthioacetic acid (2b) (0.20 g, 1.1 mmol) in 7 mL of AcOH
was refluxed for 5 h and filtered. Methanol (3 mL) was added to
the hot mother liquor. The resulting mixture was cooled with ice
and the precipitate that formed was filtered off, washed with
MeOH (2 mL), dried in air, and recrystallized from ethyl acꢀ
etate (20 mL)—light petroleum (10 mL) to give colorless crystals,
m.p. 237—240 °C. The yield of compound 3b was 0.16 g (23%).
Found (%): C, 62.14; H, 4.59; N, 5.87; S, 13.50. C36H31N3O6S3.
Calculated (%): C, 61.96; H, 4.48; N, 6.02; S, 13.78.
13ꢀ(2ꢀCarboxyethyl)ꢀ6,12ꢀepiminoꢀ5,11ꢀditosylꢀ5,6,11,12ꢀ
tetrahydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (3c). A mixture of aldeꢀ
hyde 1 (1.37 g, 5 mmol) and βꢀalanine (2c) (0.45 g, 5 mmol) in
10 mL of PrOH was refluxed for 3 h. Then a mixture of EtOH
(15 mL) and water (10 mL) was added. The resulting mixture was
brought to boiling, filtered hot, and cooled in ice. The precipitate
2ꢀMesylaminobenzoic acid mesylhydrazide (5). Mesyl chloꢀ
ride (40 mL, 0.52 mol) was added in small portions to a stirred
mixture of anthranilohydrazide (38 g, 0.25 mol) and pyridine

2268
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 10, October, 2004
Ukhin and Kuz´mina
(90 mL), which was accompanied by the increase in the temꢀ
perature of the mixture almost to boiling. The reaction mixture
was refluxed for 30 min, cooled, diluted with an equal volume of
MeOH and 30 mL of water, and kept in ice. The precipitate that
formed was filtered off, washed with water, 30% EtOH (25 mL),
and 50% EtOH (25 mL), and dried in air. The yield of comꢀ
pound 5 was 47 g (62%), m.p. 205 °C (from PriOH). Found (%):
C, 34.82; H, 4.57, N, 13.44; S, 21.17. C9H13N3O5S2. Calcuꢀ
lated (%): C, 35.17; H, 4.26, N, 13.67; S, 20.86.
2ꢀMesylaminobenzaldehyde (6). Anhydrous Na2CO3 (34 g,
0.32 mol) was added in small portions at 155 to 165 °C to a
stirred solution of hydrazide 5 (34 g, 0.12 mmol) in 125 mL of
ethylene glycol. The reaction mixture was kept at this temperaꢀ
ture until the gas ceased to evolve completely (~30 min) and
then cooled to 70—80 °C. The precipitate was filtered off and
the filtrate was poured into a mixture of ice (150 g) and water
(100 mL). Acetic acid (10 mL) was added to the resulting transꢀ
parent solution, which was then left in a refrigerator for 12 h.
The sticky precipitate that formed was separated and refluxed in
20 mL of PriOH to give a friable powder. On cooling, the mixꢀ
ture was kept in ice for 1 h and the precipitate was filtered off,
washed with cold PriOH (2×5 mL) and light petroleum (5 mL).
The crude product was dissolved in 20 mL of cold CHCl3; the
undissolved part was filtered off and washed with CHCl3. The
solvent was evaporated to dryness and the crystalline residue was
washed with cold PriOH (3 mL) and light petroleum (3 mL) and
dried to give colorless crystals, m.p. 120 °C (from PriOH). The
yield of compound 6 was 3.0 g (14%). Found (%): C, 48.17;
H, 4.69, N, 7.21; S, 16.40. C8H9NO3S. Calculated (%): C, 48.23;
H, 4.55, N, 7.03; S, 16.09.
The precipitate that formed was filtered off and chromatographed
on Al2O3 in CHCl3 to give compound 7d (0.11 g, 16%), colorless
crystals, m.p. 247—250 °C. Found (%): C, 57.92; H, 4.93,
N, 9.37; S, 13.82. C22H21N3O4S2. Calculated (%): C, 58.00;
H, 4.65, N, 9.22; S, 14.08.
6,12ꢀEpiminoꢀ5,11ꢀdimesylꢀ13ꢀpꢀtolylꢀ5,6,11,12ꢀtetraꢀ
hydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (7e). A mixture of aldehyde 6
(0.4 g, 2 mmol) and pꢀtoluidine (0.11 g, 1.0 mmol) in 3 mL of
AcOH was refluxed for 4 h and cooled. A resinous product was
precipitated with water, separated, dissolved in CHCl3, and
passed through a column with Al2O3. The solvent was removed
and the resulting oil solidified upon trituration with light petroꢀ
leum. The precipitate was filtered off and recrystallized from
PriOH (12 mL) to give compound 7e (0.07 g, 15%), colorless
substance, m.p. 212—215 °C. Found (%): C, 58.73; H, 5.20,
N, 9.13; S, 14.00. C23H23N3O4S2. Calculated (%): C, 58.85;
H, 4.94, N, 8.95; S, 13.63.
Xꢀray diffraction analysis of compounds 3a—c. Single crysꢀ
tals covered with a perfluorinated oil were placed in a Bruker
SMARTꢀCCD diffractometer under a flow of cooled nitrogen.
Sets of experimental reflections were collected in the ωꢀscan
mode (MoꢀKα radiation). Crystallographic parameters and a
summary of data collection for compounds 3a—c are given in
Table 4. The experimental reflections were refined with the
Bruker SAINT program package.6
The structures were solved by the direct methods and refined
by the leastꢀsquares method in the fullꢀmatrix anisotropic
approximation on F2. In all cases, hydrogen atoms were
located from the electronꢀdensity difference maps and reꢀ
fined isotropically. All calculations were performed with the
SHELXTLꢀPlus program package.7
6,12ꢀEpiminoꢀ5,11ꢀdimesylꢀ5,6,11,12ꢀtetrahydrodibenꢀ
zo[b, f ]ꢀ1,5ꢀdiazocine (7a). A mixture of aldehyde 6 (0.6 g,
3 mmol) and NH4OAc (0.2 g, 2.5 mmol) in 5 mL of PrOH was
refluxed for 2 h and cooled in ice. The precipitate that formed
was filtered off and recrystallized from MeOH (75 mL) to give
colorless crystals, m.p. 220 °C. The yield of compound 7a was
0.14 g (25%). Found (%): C, 50.21; H, 4.83, N, 10.92; S, 17.26.
C16H17N3O4S2. Calculated (%): C, 50.65; H, 4.52, N, 11.07;
S, 16.90.
Atomic coordinates and other experimental data were deꢀ
posited with the Cambridge crystallographic data collection
(CCDC, 12 Union Road, Cambridge CB21EZ, UK; fax:
(+44)1223ꢀ336ꢀ033; eꢀmail: deposit@ccdc.cam.ac. The regisꢀ
tration numbers are CCDCꢀ232632 (3a), 232633 (3b), and
232634 (3c)).
References
6,12ꢀEpiminoꢀ5,11ꢀdimesylꢀ13ꢀmethylꢀ5,6,11,12ꢀtetraꢀ
hydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (7b). A mixture of aldehyde 6
(0.6 g, 3 mmol), MeNH2•HCl (0.1 g, 1.5 mmol), and NaOAc
(0.12 g, 1.5 mmol) in 5 mL of PrOH was refluxed for 2.5 h. The
reaction mixture was diluted with water (20 mL) and the preꢀ
cipitate that formed was filtered off and recrystallized from
PriOH. The unconsumed aldehyde 6 was separated by column
chromatography on Al2O3 in CHCl3. The yield of compound 7b
was 0.2 g (34%), colorless crystals, m.p. 227—230 °C. Found (%):
C, 51.72; H, 5.05, N, 10.41; S, 15.96. C17H19N3O4S2. Calcuꢀ
lated (%): C, 51.89; H, 4.87, N, 10.68; S, 16.30.
6,12ꢀEpiminoꢀ13ꢀethylꢀ5,11ꢀdimesylꢀ5,6,11,12ꢀtetrahydroꢀ
dibenzo[b, f ]ꢀ1,5ꢀdiazocine (7c) was obtained analogously from
aldehyde 6 (0.6 g, 3 mmol), EtNH2•HCl (0.15 g, 1.8 mmol),
and NaOAc (0.15 g, 1.8 mmol). The yield of compound 7c was
0.2 g (32%), colorless crystals, m.p. 205—207 °C. Found (%):
C, 53.21; H, 5.34, N, 10.07; S, 15.50. C18H21N3O4S2. Calcuꢀ
lated (%): C, 53.05; H, 5.19, N, 10.31; S, 15.73.
1. L. Yu. Ukhin, V. N. Komissarov, I. A. Litvinov, V. A. Piven´,
and N. A. Litvinova, Dokl. Akad. Nauk SSSR, 1988, 303, 646
[Dokl. Chem., 1988 (Engl. Transl.)].
2. L. Yu. Ukhin, Zh. I. Orlova, and V. N. Khrustalev, Izv. Akad.
Nauk, Ser. Khim., 1997, 2035 [Russ. Chem. Bull., 1997, 46,
1931 (Engl. Transl.)].
3. B. M. Bolotin, D. A. Drabkina, V. G. Brudz´, and A. S.
Kurnosov, Metody polucheniya khimreaktivov i preparatov
[Methods for the Synthesis of Chemicals and Preparations],
IREA, Moscow, 1964, No. 9, 12 (in Russian).
4. N. I. Chernova, Yu. S. Ryabokobylko, V. G. Brudz´, and
B. M. Bolotin, Zh. Org. Khim., 1971, 7, 1680 [J. Org. Chem.
USSR, 1971, 7 (Engl. Transl.)].
5. Technique of organic chemistry, Ed. A. Weissberger, Interꢀ
science Publishers, New York.
6. SAINT, Version 6.02A, Bruker AXS Inc., Madison (Wisconꢀ
sin, USA), 2001.
7. SHELXTLꢀPlus, Release 5.10, Bruker AXS Inc., Madison
(Wisconsin, USA), 1997.
6,12ꢀEpiminoꢀ5,11ꢀdimesylꢀ13ꢀphenylꢀ5,6,11,12ꢀtetraꢀ
hydrodibenzo[b, f ]ꢀ1,5ꢀdiazocine (7d). A mixture of aldehyde 6
(0.6 g, 3 mmol) and aniline (0.14 g, 1.5 mmol) in 5 mL of AcOH
was refluxed for 8 h, cooled, and diluted with water (20 mL).
Received April 19, 2004;
in revised form June 28, 2004