En route to molecular bracelets: The synthesis of linear pentacyclic bis(benzodiazocino)benzenes

Article abstract of DOI:10.1055/s-2000-6392

The title compounds, namely dibenzo[b,b']benzo[1,2-f:4,5- f']bis[1,5]diazocines, have been synthesized in a single step in two alternative ways by application of the 'tertiary amino effect': (i) the action of bis-Vilsmeier reagents derived from N,N'-dimethyl-N,N'-diformyl-p- phenylenediamine upon 4-substituted N,N-dimethylanilines, and (ii) the action of Vilsmeier reagents derived form 4-substituted N-methylformanilides on bis(dimethylamino)benzenes.

Full text of DOI:10.1055/s-2000-6392

640
SHORT PAPER
En Route to Molecular Bracelets: The Synthesis of Linear Pentacyclic
Bis(benzodiazocino)benzenes
Ying Cheng,a* Qing−Xiang Liu,a Otto Meth−Cohnb*
aDepartment of Chemistry, Beijing Normal University, Beijing 100875, China
bDepartment of Chemistry, University of Sunderland, Sunderland SR1 3SD, UK
Fax: +44(191)5152587; E-mail: otto.meth-cohn@sunderland.ac.uk
Received 5 January 2000
Abstract: The title compounds, namely dibenzo[b,b′]benzo[1,2-
f:4,5-f′]bis[1,5]diazocines, have been synthesised in a single step in
two alternative ways by application of the ‘tertiary amino effect’: (i)
the action of bis-Vilsmeier reagents derived from N,N′-dimethyl-
N,N′-diformyl-p-phenylenediamine upon 4-substituted N,N-di-
methylanilines, and (ii) the action of Vilsmeier reagents derived
form 4-substituted N-methylformanilides on bis(dimethylami-
no)benzenes.
Key words: Vilsmeier, bisdiazocines, bracelets
In earlier work, we established a simple one-pot reaction
for the synthesis of 5,6,11,12-tetrahydrodiben-
zo[b,f][1,5]diazocines1 by the treatment of 4-substituted
N,N-dimethylanilines with N-methylformanilides in
POCl3 (Scheme 1). These systems are known2 to prefer a
boat conformation and consequently we envisaged that
larger assemblies of linear fused analogues could be of in-
terest in the synthesis of novel macrocycles such as ‘mo-
lecular bracelets’. To this end, we have now extended this
methodology to the synthesis of 5,6,8,9,14,15,17,18-oc-
tahydrodibenzo[b,b′]benzo[1,2-f:4,5-f′]bis[1,5]diazo-
cines 4, a novel linear pentacyclic heterocycle.
Scheme 2
The same product 4 could also be obtained by treatment
of 1,4-bis(dimethylamino)benzene 6 with the Vilsmeier’s
reagents 7 derived from a 4-substituted N-methylform-
anilide and oxalyl chloride, though yields were lower
(~15%) (Scheme 2).
Table 1 Preparation and Properties of Compounds 4 and 5
Starting Prod- Reaction Yield
Materials uct Method (%)
Mp
Molecular
Formula
(oC)
Scheme 1
1 and 3
1 and 3
1 and 3
1 and 3
1 and 3
1 and 3
1 and 3
1 and 3
6 and 7
6 and 7
4a
4b
4c
5c
4d
5d
4e
5e
4d
4e
A
A
A
A
A
A
A
A
B
B
40
56
22
36
52
13
23
30
13
15
227-229 C28H34N4
238-240 C28H34N4O2
239-241 C26H28N4F2
166-168 C18H20N3FO
When treated with oxalyl chloride in chloroform, N,N′-
dimethyl-N,N′-diformyl-p-phenylenediamine 1 formed a
solid Vilsmeier reagent 2, which reacted with 4-substitut-
ed N,N′-dimethylanilines 3 on heating to reflux in chloro-
form for 10−11 hours. After basic work-up
dibenzo[b,b′]benzo[1,2-f;4,5-f′]bis[1,5]diazocines 4 were
obtained in 22−56% yield (Scheme 2, Table 1−2). In some
cases, a half-cyclized product 5 was also obtained in 13−
36% yield. The formation of the half-cyclized product 5
was probably due to the incomplete conversion of the for-
manilide 1 into the bis-Vilsmeier reagent.
> 300
C26H28N4Cl2
210-212 C18H20N3ClO
282-283 C26H28N4Br2
212-214 C18H20N3BrO
Synthesis 2000, No. 5, 640–642 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
The Synthesis of Linear Pentacyclic Bis(benzodiazocino)benzenes
641
Table 2 Spectroscopic Data for Compounds 4 and 5
Compounda
IR (KBr)
1H NMR (CDCl3)
d (ppm), J (Hz)
13C NMR (CDCl3)
d (ppm)
MS
m/z (%)
v (cm−1)
4a
1620 (w),
1520 (s)
7.00 (d, 2 H, J = 8.0), 6.95 (s, 1 H), 6.85
(br s, 1 H), 4.14-4.35 (br, 4 H, NCH2),
2.87 (br s, 6 H, NCH3), 2.27 (br s, 3 H,
ArMe)
148.9, 143.7, 132.1, 128.4, 128.0,
127.4, 120.4, 115.7, 59.1, 58.8,
40.0, 39.5, 20.3
426 (M+, 100)
458 (M+, 100)
434 (M+, 100)
4b
1600 (w),
1500 (s),
1040 (m)
7.21 (br s, 1 H), 6.77 (d, 2 H, J = 8.7), 6.72
(s, 1 H), 4.16-4.39 (br, 4 H, 2NCH2),
3.77 (s, 3 H, OCH3), 2.87 (br s, 6 H,
2NCH3)
125.7, 145.7, 144.1, 130.3, 128.9,
120.3, 117.4, 112.8, 59.3, 59.2,
55.8, 40.0, 39.9
4c
1620 (w),
1520 (s)
6.89-6.90 (m, 4 H), 4.10-4.70 (br, 4 H,
NCH2), 2.87 (br s, 6 H, NCH3)
4d
1590 (w),
1500 (s)
7.25 (s, 1 H), 7.23 (d, 1 H, J = 6.7), 6.92-
7.00 (m, 2 H), 4.35-4.41 (br, 4 H, NCH2),
2.97 (br s, 6 H, NCH3)
466 (100) / 468
(68) / 470 (13)
(M+)
4e
5c
1610, 1520
7.34 (d, 1 H, J = 8.7), 7.31 (s, 1 H), 7.05
(s, 1 H), 6.91 (d, 1 H, J = 8.5), 4.47 (s,
2 H, NCH2), 4.38 (s, 2 H, NCH2), 3.06 (s,
3 H, NCH3), 2.93 (s, 3 H, NCH3)
554 (51)/556
(100)/558 (50)
(M+)
1660 (s) (C=O),
1520 (s),
1500 (s)
8.35 (s, 1 H, CHO), 7.04 (s, 2 H), 6.92-
6.99 (m, 2 H), 6.87 (dd, 2 H, J = 8.6, 2.8),
4.47 (s, 2 H, NCH2), 4.41 (s, 2 H, NCH2),
3.24 (s, 3 H, NCH3), 3.02 (s, 6 H, NCH3)
162.4, 157.8, 154.2, 149.5, 146.9,
133.0, 128.6/128.5/128.2 (t),
126.6, 123.3, 117.7/117.4/117.1/
117.0 (q), 116.3, 114.5/114.2 (d),
58.5, 58.1, 39.5, 39.2, 32.7
313 (M+, 100)
5d
5e
1660 (s) (C=O),
1520 (s),
1500 (s)
8.36 (s, 1 H, CHO), 6.85-7.17 (m, 6 H,),
4.31 (s, 2 H, NCH2), 4.29 (s, 2 H, NCH2),
3.27 (s, 3 H, NCH3), 2.88 (s, 3 H, NCH3),
2.85 (s, 3 H, NCH3)
162.4, 149.3, 149.0, 132.8, 131.0,
127.9, 127.5, 126.7, 123.4, 122.8,
116.6, 116.5, 116.1, 58.2, 57.9,
39.1, 32.7, 30.7
329 (100) / 331
(33) (M+)
1670 (s) (C=O),
1520 (s),
1500 (s)
8.26 (s, 1 H, CHO), 6.79-7.31 (m, 6 H),
4.30 (s, 4 H, 2NCH2), 3.27 (s, 3 H,
NCH3), 2.91 (s, 3 H, NCH3), 2.84 (s, 3 H,
NCH3)
161.0, 148.3, 147.8, 132.5, 131.4,
129.5, 127.3, 126.1, 125.4, 122.0,
115.8, 114.8, 108.3, 56.7, 56.5,
37.9, 31.4, 28.3
373 (100)/375
(98) (M+), 189
(48), 177 (51),
117 (59)
a All compounds gave satisfactory elemental analysis; C, 0.49; H, 0.21; N, 0.40
The bis-(benzodiazocino)benzenes 4 are insoluble both in
(10.8 g, 0.1 mol) was added with cooling in an ice-water bath. The
mixture was stirred at 80−90 °C for 2 h, H2O was added and the pre-
cipitate filtered, washed with H2O and dried. Recrystallization from
MeOH gave N,N′-diformylphenylenediamine in 60% yield, mp
204−206 °C [Lit.3 204−205 °C]. IR: vc=o= 1680 cm−1.
water and in most organic solvents such as DMSO, meth-
anol, acetone, acetonitrile and ethyl acetate. They are
slightly soluble in CHCl3 forming a yellow solution. It is
interesting that the yellow chloroform solution turns to
blue on exposure to light. The blue solution changes back To N,N′-diformylphenylenediamine (8.2 g, 0.05 mol) in dry DMF
(50 mL) was added NaH (2.4 g, 0.06 mol, 60% in paraffin) under
N2 atm with ice-bath cooling. After gas evolution ceased, MeI (8.46
g, 0.06 mol) in dry DMF (20 mL) was added dropwise and the mix-
ture stirred at 80 °C for 2 h, and then at r.t. for 24 h. After removal
to yellow when it is kept in the dark for a few minutes. We
believe the bis-diazocinobenzenes 4 will prove to be ef-
fective building blocks in the construction of supramolec-
ular systems and this work is ongoing.
of the DMF under vacuum, H2O was added (150 mL) and the prod-
uct 1 filtered, washed with H2O and dried, and further purified by
recrystallization from EtOH (71%). Mp 199−201 °C. [Lit.3 201−
Mps are uncorrected. 1H and 13C NMR spectra in CDCl3 were ob-
202 °C]. IR: vc=o = 1680 cm−1.
1H NMR: δ (ppm) = 8.51 (s, 2H, CHO); 7.41 (s, 4H, PhH); 3.21 (s,
tained on a Varian Unity 200 MHz and 300 MHz spectrometers. IR
spectra were recorded with a HITACHI-260-50 spectrometer. Mass
spectra were recorded with a KYKY-ZHT-5 instrument. Elemental
6H, NCH3).
analyses were performed on a Perkin−Elmer 240C instrument.
5,6,8,9,14,15,17,18-Octahydro-5,8,14,17-tetramethyl-2,11-di-
substituted dibenzo [b,b′]benzo[1,2-f:4,5- f′]bis[1,5]diazocines
4, and 5,6,11,12-tetrahydro-5,11-dimethyl-8-halogen-2-(N-me-
N, N′-Dimethyl-N, N′- diformyl-p-phenylenediamine (1)
Formic acid (>98%, 23 g, 0.5 mol) and acetic anhydride (51 g, 0.5
mol) were mixed and warmed for 2 h at 60 °C. p-Phenylenediamine
Synthesis 2000, No. 5, 640–642 ISSN 0039-7881 © Thieme Stuttgart · New York

642
Y. Cheng et al.
SHORT PAPER
thyl-N-formylamino)dibenzo[b,f][1,5]diazocines 5; General
Procedure
up was as for method A, and the products and their properties are
recorded in Tables 1 and 2.
Method A: To N,N′-dimethyl-N,N′-diformylphenylenediamine (1)
(1.92 g, 0.01 mol) was added oxalyl chloride (2 mL) under N2. The
mixture was stirred for 30 min at r.t., dry CHCl3 (30 mL) was then
added, and stirring continued for 1 h at 40−50 °C. The mixture was
cooled in an ice-bath while a solution of 4-substituted N,N-dimeth-
ylaniline 3 (0.02 mol) in dry CHCl3 (30 mL) was added dropwise.
The resulting red brown solution was then refluxed for 11 h. After
removal of the solvent, the residue was basified with aq NaOH
(10%) to pH 9−10. In the case of the halo derivatives, addition of
CHCl3 (100 mL) caused precipitation of the bis-benzodiazocines 4,
while the products 5 dissolved in the solvent. The bis-benzodiazo-
cines 4 were filtered and recrystallised from CHCl3/CH3OH. The
products 5 were obtained by drying (MgSO4), evaporating the
CHCl3 solution, and purified by chromatography. The products 4
(X = Me, OMe) were isolated by chromatography and purified fur-
ther by recrystallization from EtOAc. The products and their prop-
erties are recorded in Tables 1 and 2.
Acknowledgement
This work was supported by the National Natural Science Founda-
tion of China to whom we are most grateful (Grant No. 29772003).
References
(1) Meth−Cohn, O.; Taylor, D. L. J. Chem. Soc., Chem.
Commum. 1995, 1463.
Cheng, Y; Meth−Cohn, O.; Taylor; D. L. J. Chem. Soc.,
Perkin Trans. 1 1998, 1257.
(2) Crossley, R.; Downing, A. P.; Nogradi, M.; Braga de Oliviera,
A.; Ollis, W. D.; Sutherland, I. O. J. Chem. Soc., Perkin Trans.
1 1998, 1257.
(3) Sekiya, M.; Takayama, S.; Ito, K.; Suzuki, J.; Suzuki, K.;
Terao, Y. Chem. Pharm. Bull. 1972, 20, 2661.
Method B: The 4-substituted N-methylformanilide 7 (0.02 mol) was
mixed with oxalyl chloride (2 mL) under N2 with cooling in an ice-
bath to form a red solution. N,N,N′N′-Tetramethyl-p-phenylenedi-
amine (6) in dry CHCl3 (50 mL) was then added dropwise. The mix-
ture was refluxed for 11 h and after removal of the solvent, the
residue was basified with aq NaOH (10%) to pH 9−10. The work-
Article Identifier:
1437-210X,E;2000,0,05,0640,0642,ftx,en;P00400SS.pdf
Synthesis 2000, No. 5, 640–642 ISSN 0039-7881 © Thieme Stuttgart · New York