Synthesis of 4,5-dihydro-1,6:3,8-dimethano-1,3,6,8-benzotetrazecine

Article abstract of DOI:10.1007/s11172-008-0205-6

Three-component condensation of formaldehyde, o-phenylenediamine, and ethylenediamine gave for the first time 4,5-dihydro-1,6:3,8-dimethano-1,3,6,8- benzotetrazecine. Its structure was proved by X-ray diffraction analysis. A similar condensation of formaldehyde with a mixture of ethylenediamine and 1,2-diamino-4-methylbenzene yielded 10-methyl-4,5-dihydro-1,6:3,8-dimethano-1,3, 6,8-benzotetrazecine and a condensation with a mixture of o-phenylenediamine and propane-1,2-diamine yielded 4-methyl-4,5-dihydro-1,6:3,8-dimethano-1,3,6,8- benzotetrazecine.

Full text of DOI:10.1007/s11172-008-0205-6

Russian Chemical Bulletin, International Edition, Vol. 57, No. 7, pp. 1575—1577, July, 2008
1575
Synthesis of 4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenzotetrazecine
A. I. Kuznetsov,a A. H. Shukkur, and K. Kamarab
b
aM. V. Lomonosov Moscow State Academy of Fine Chemical Technology,
8
6 prosp. Vernadskogo, 119571 Moscow, Russian Federation.
Eꢀmail: tetraza@mail.ru
b
University of Anbar, Ramadi, Al Anbar, Iraq.
Eꢀmail: Ahmed73@mail.ru
Threeꢀcomponent condensation of formaldehyde, oꢀphenylenediamine, and ethylenediamine
gave for the first time 4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenzotetrazecine. Its structure was
proved by Xꢀray diffraction analysis. A similar condensation of formaldehyde with a mixture of
ethylenediamine and 1,2ꢀdiaminoꢀ4ꢀmethylbenzene yielded 10ꢀmethylꢀ4,5ꢀdihydroꢀ1,6:3,8ꢀdiꢀ
methanoꢀ1,3,6,8ꢀbenzotetrazecine and a condensation with a mixture of oꢀphenylenediamine and
propaneꢀ1,2ꢀdiamine yielded 4ꢀmethylꢀ4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenzotetrazecine.
Key words: oꢀphenylenediamine, 1,2ꢀdiaminoꢀ4ꢀmethylbenzene, ethylenediamine, propaneꢀ
1,2ꢀdiamine, formaldehyde, Xꢀray diffraction analysis, condensation.
For design and synthesis of complex polycyclic frameꢀ
work molecules, first one should realize how several
simple molecules organize themselves into a larger one.
In 1860, A. M. Butlerov discovered condensation of formꢀ
aldehyde with ammonia in the ratio 6 : 4 into hexamethꢀ
ylenetetramine, the reaction producing no other stable
products. Previously, we have found that a mixture of
these reagents and aromatic 1,2ꢀdiamines yields, along
with hexamethylenetetramine and condensation products
from formaldehyde and diamines, products of threeꢀcomꢀ
ponent condensation of formaldehyde, ammonia, and
aromatic 1,2ꢀdiamines. It was interesting to try to replace
ammonia by aliphatic diamines in this reaction.
Scheme 1
1
2
We discovered that a reaction of formaldehyde with
a mixture of ethylenediamine and oꢀphenylenediamine
gives not only formaldehyde—diamine condensation
products but also 4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ
R = R´ = H (а); R = Ме, R´ = H (b); R = H, R´ = Ме (c)
2
3—7
1
,3,6,8ꢀbenzotetrazecine (1a) via threeꢀcomponent conꢀ
2a, 2b, and 3,
respectively. Condensation of formalꢀ
densation (Scheme 1). Using 1,2ꢀdiaminoꢀ4ꢀmethylꢀ
benzene instead of oꢀphenylenediamine, we obtained
dehyde with propaneꢀ1,2ꢀdiamine yielded a mixture of
liquid products easily separable from the target crystalꢀ
8
1
0ꢀmethylꢀ4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenꢀ
line product 1c.
zotetrazecine (1b). Its isomer containing the Me group in
the ethylene bridge rather than in the benzene ring
(
4ꢀmethylꢀ4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenꢀ
zotetrazecine (1c)) was obtained as a racemate by conꢀ
densation of formaldehyde, oꢀphenylenediamine, and
propaneꢀ1,2ꢀdiamine.
The structures of compounds 1a—c were confirmed
1
by elemental analysis data and H NMR and mass spectra.
Parallel twoꢀcomponent condensation reactions of
formaldehyde with oꢀphenylenediamine, 1,2ꢀdiaminoꢀ
4
ꢀmethylbenzene, and ethylenediamine gave compounds
R = H (a), Mе (b)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1544—1546, July, 2008.
066ꢀ5285/08/5707ꢀ1575 © 2008 Springer Science+Business Media, Inc.
1

1
576
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 7, July, 2008
Kuznetsov et al.
We also developed a simplified procedure for the
synthesis of product 3 from ethylenediamine and formalꢀ
dehyde.
M/ΔM = 10 000. The injector temperature was 20 °C. The course of
the reactions was monitored and the purity of the products was
checked by TLC on Silufol UVꢀ254 plates. Spots were visualized
with the iodine vapor in a moist chamber or under UV light.
The structure of compound 1a was determined from
Xꢀray diffraction data (Fig. 1). Its geometrical parameꢀ
ters are comparable with those for compounds 2a (see
Ref. 4) and 3 (see Ref. 5), which suggests their structural
similarity.
4
,5ꢀDihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenzotetrazecine
(
1a). Paraformaldehyde (3.3 g, 108 mmol) was added in small
portions to a stirred solution of oꢀphenylenediamine (3.0 g, 27
mmol) and ethylenediamine (2 mL, 27 mmol) in hexane (20 mL).
The reaction mixture was heated to complete homogenization. The
organic layer was separated by decanting and the product was
extracted from the aqueous layer with hot hexane (4×20 mL). The
combined extracts were concentrated and the residue was recrystalꢀ
lized successively from water and isopropyl alcohol. The yield was
2
The C(sp )—N bond lengths in structure 1a (1.437 Å)
3
equal those in structure 2a. The C(sp )—N bond lengths
in structures 1a and 3 are 1.464 and 1.470 Å, respectively.
The angles N—C—N (the mean is 118.8°) and the angles
C—N—C (they range from 112.2° to 115.6°; the mean is
1
.0 g (17%), white crystals, m.p. 103—104 °C (subl.). Found (%):
C, 65.57; H, 7.03; N, 27.40. C H N . Calculated (%): C, 65.63;
1
2
16
4
1
14.3°) are comparable with those in 1,3,6,8ꢀtetraꢀ
1
H, 6.97; N, 27.70. H NMR, δ: 3.40 (s, 4 H, NCH CH N); 4.20
d, 8 H, 4 NCH N, J = 13.5 Hz); 7.18 (s, 4 H, C H ). MS, m/z
2 6 4
Irel (%)): 216 [M] (48), 174 (24), 147 (22), 131 (100), 118 (46),
2
2
3
,8
azatricyclo[4.4.1.1 ]dodecane (3) (the mean values of
the angles N—C—N and C—N—C are 118.6° and 114.8°,
respectively).
2
(
(
+
104 (45), 85 (43), 77 (51), 55 (69), 51 (35).
Compounds 1a—c belong to a specific group of aroꢀ
matic amines in which the lone electron pairs on the N
atoms bound to the benzene ring cannot efficiently interꢀ
act with its electron system because of geometrical factors.
Table 1. Selected crystallographic parameters and a summary of data
collection for structure 1a
Parameter
Value
Experimental
Molecular formula
C H N
4
12
16
M
216.29
0.21×0.24×0.35
Monoclinic
1H NMR spectra were recorded on a Bruker WMꢀ500 specꢀ
Crystal size/mm
trometer (500.13 MHz) for 2—3% solutions in CDCl . Mass specꢀ
3
Crystal system
Space group
a/Å
b/Å
c/Å
tra were recorded on a Finnigan MATꢀ90 instrument (direct inlet
probe, voltage 5.0 kV, cathode emission current 100 μA, ionizing
electron energy 70 eV, ionization chamber temperature 200 °C).
Perfluorokerosene was used as a standard. The resolution was
P2 /c
1
12.090(2)
16.092(3)
12.533(3)
α/deg
β/deg
γ/deg
V/Å3
90
113.27(3)
C(10)
90
2240.0(8)
C(9)
N(2)
N(4)
Z
8
–
3
dcalc/g cm
μMo/mm
F(000)
Diffractometer
T/K
Radiation (λ/Å)
1.283
0.081
928
C(11)
–1
«Enraf—Nonius CADꢀ4»
293
MoꢀKα (0.71073),
graphite monochromator
ω
2.17—27.90
–15 < h < 1, 0 < k < 21,
–14 < l < 16
2343
C(12)
C(7)
N(3)
N(1)
Scan mode
Range of θ/deg
Ranges of h, k, l indices
C(8)
C(2)
Number of measured
reflections
Number of independent
reflections
Number of parameters
refined
GOOF по F2
C(1)
C(3)
2130
(Rint = 0.0206)
289
C(6)
0.659
R (I > 2σ(I))
R = 0.0371, wR = 0.1023
1
2
R (for all reflections)
Residual electron
density (max/min)/e Å–3
R = 0.0382, wR = 0.1029
1
2
C(4)
0.127/–0.188
C(5)
Fig. 1. Structure 1a.

4
,5ꢀDihydroꢀ1,6:3,8ꢀdimethanobenzotetrazecine
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 7, July, 2008
1577
1
0ꢀMethylꢀ4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenꢀ
zotetrazecine (1b). 1,2ꢀDiaminoꢀ4ꢀmethylbenzene (3.0 g,
4.6 mmol) and ethylenediamine (1.72 mL, 24.6 mmol) were
by the leastꢀsquares method in the fullꢀmatrix anisotropic approxiꢀ
mation for all nonꢀhydrogen atoms. The H atoms were located
geometrically and refined in the rider model with fixed isotropic
2
2
dissolved with heating in water (10 mL). The resulting solution was
mixed with light petroleum (20 mL). Paraformaldehyde (2.95 g,
8.4 mmol) was added in small portions to the stirred mixture,
which was heated to complete homogenization. The organic layer
was separated by decanting and the product was extracted from
the aqueous layer with hot light petroleum (4×20 mL). The comꢀ
bined extracts were concentrated and the residue was recrystallized
successively from water and light petroleum. The yield was 1.5 g
27%), white crystals, m.p. 115—116 °C (subl.). Found (%):
C, 67.32; H, 7.55; N, 24.80. C H N . Calculated (%): C, 67.79;
H, 7.87; N, 24.32. H NMR, δ: 2.35 (s, 3 H, Me); 3.45 (s, 4 H,
NCH CH N); 4.25 (d, 8 H, 4 NCH N, J = 13.5 Hz); 7.00 (m, 3 H,
thermal parameters (Uiso = 0.08 Å ). The calculations were perꢀ
formed with the SHELXꢀ86 (see Ref. 9) and SHELXꢀ93 proꢀ
10
9
grams. Comprehensive Xꢀray diffraction data have been deposited
with the Cambridge Crystallographic Data Center.
We are grateful to Yu. E. Gorbunova for her assisꢀ
tance in Xꢀray diffraction analysis.
This work was financially supported by the Moscow
Committee for Science and Technologies (Grant 1.1217
(2004)) and the Ministry of Education and Science of the
Russian Federation (Grant 1Bꢀ18ꢀ329 (2005)).
(
13
18
4
1
2
2
2
2
+
C H ). MS, m/z (I (%)): 230 [M] (12), 202 (4), 147 (9),
6
3
rel
146 (49), 145 (100), 132 (14), 119 (8), 70 (10), 67 (10), 56 (39), 42 (77).
References
4
ꢀMethylꢀ4,5ꢀdihydroꢀ1,6:3,8ꢀdimethanoꢀ1,3,6,8ꢀbenzotetrꢀ
azecine (1c). Paraformaldehyde (7.0 g, 230 mmol) was added in
small portions to a solution of oꢀphenylenediamine (3.35 g, 60 mmol)
and propaneꢀ1,2ꢀdiamine (4.35 g, 60 mmol) in light petroleum
1
. A. M. Butlerov, Gorn. Zh., 1860, 4, 461 [A. M. Butlerov,
Izbrannye raboty [Selected Works], Izd. Akad. Nauk SSSR,
Moscow, 1951, 55] (in Russian).
. A. I. Kuznetsov, A. H. Shukkur, K. Kamara, Izv. Akad. Nauk,
Ser. Khim., 2007, 542 [Russ. Chem. Bull., Int. End., 2007,
(20 mL). The reaction mixture was stirred for 30 min. The organic
2
layer was separated by decanting and the product was extracted from
the residue with light petroleum (3×20 mL). The combined extracts
were concentrated and the residue was recrystallized from hexane.
The yield was 3.0 g (22%), white crystals, m.p. 90—91 °C.
Found (%): C, 67.32; H, 7.55; N, 24.80. C H N . Calculated
5
6, 563].
3
4
. A. Rivera, J. RiosꢀVotta, Tetrahedron Lett., 2005, 46, 5001.
. P. MurrayꢀRust, I. Smith, Acta Crystallogr., 1975, 31B, 587.
1
3
18
4
5. P. MurrayꢀRust, F. G. Riddel, J. Chem. Soc., Perkin Trans. 2,
974, 10, 1433.
6. G. Volpp, Chem. Ber., 1962, 95, 1493.
7. M. I. Shakhgel´diev, G. B. Babieva, O. G. Nabiev, R. G.
Kostyanovskii, Khim. Geterotsikl. Soedin., 1987, 712 [Chem.
Heterocycl. Compd., 1987 (Engl. Transl.)].
8
9
1
(
%): C, 67.79; H, 7.87; N, 24.32. H NMR, δ: 1.25 (d, 3 H, Me,
1
J = 7.8 Hz); 3.60 (m, 1 H, NCHCH ); 2.90, 3.70 (both dd, 2 H,
2
NCH C, J = 7.2 Hz, J = 15.0 Hz, J = 9.6 Hz, J = 15.0 Hz); 4.20
2
(
(
1
d, 8 H, 4 NCH N, J = 15.6 Hz); 7.15 (s, 4 H, C H ). MS, m/z
2 6 4
+
Irel (%)): 230 [M] (36), 160 (17), 133 (69), 132 (72), 131 (100),
18 (36), 104 (22), 97 (100), 78 (51), 77 (55), 56 (21).
,3,6,8ꢀTetraazatricyclo[4.4.1.13,8]dodecane (3). Paraformꢀ
. J. Hocker, D. Wendisch, J. Chem. Res. S, 1977, 236.
. G. M. Sheldrick, SHELXꢀ86, Program for the Solution of Crystal
Structures, University of Göttingen, Göttingen (Germany), 1986.
1
aldehyde (1289 g, 43 mol) was added in small portions for 6 h to
vigorously stirred ethylenediamine (1500 mL, 21.5 mol) so that the
reaction temperature was no higher than 50 °C. The reaction mixꢀ
ture was left for 12 h. The precipitate that formed was filtered off and
recrystallized from isopropyl alcohol. The yield was 1400 g (78%),
white crystals, m.p. 183—184 °C (cf. Refs 6, 7: m.p. 181—182 °C).
Xꢀray diffraction analysis. Selected crystallographic parameters
and a summary of data collection for structure 1a are given in
Table 1. The structure was solved by the direct method and refined
1
0. G. M. Sheldrick, SHELXꢀ93, Program for the Refinement of
Crystal Structures, University of Göttingen, Göttingen (Gerꢀ
many), 1993.
Received June 20, 2007;
in revised form December 25, 2007