Heterocyclic analogs of pleiadene. 71*. Synthesis of 1,3-diazapyrene

Article abstract of DOI:10.1023/A:1020977715188

The reaction of perimidine and 2-R-perimidines with α,β-unsaturated carbonyl compounds in polyphosphoric acid has yielded the previously unknown 1,3-diazapyrene and its 6,8-di- and also 2,6,8-trisubstituted derivatives. Their spectroscopic parameters are

Full text of DOI:10.1023/A:1020977715188

Chemistry of Heterocyclic Compounds, Vol. 38, No. 8, 2002
HETEROCYCLIC ANALOGS OF PLEIADENE.
71*. SYNTHESIS OF 1,3-DIAZAPYRENE
1
1
2
I. V. Borovlev , O. P. Demidov , and A. F. Pozharskii
The reaction of perimidine and 2-R-perimidines with α,β-unsaturated carbonyl compounds in
polyphosphoric acid has yielded the previously unknown 1,3-diazapyrene and its 6,8-di- and also
2
,6,8-trisubstituted derivatives. Their spectroscopic parameters are discussed.
Keywords: 1,3-diazapyrene, perimidine, polyphosphoric acid, C-alkylation.
We have previously synthesized partially hydrogenated 1,3-diazapyrene derivatives 1 which have
proved to be, in particular, good luminophores [2, 3]. However the parent heterocyclic system has remained
unknown until recent times. Meanwhile, the investigation of its aromaticity, physicochemical parameters, and
2
reactivity are of considerable interest* . In this article we describe the preparation of 1,3-diazapyrene and a
series of its simple derivatives (for preliminary report see [1]).
We have shown that the reaction of perimidine and 2-R-perimidines 2 with α,β-unsaturated ketones in
polyphosphoric acid (PPA) gives, respectively, 6,8-di and 2,6,8-trisubstituted 1,3-diazapyrenes 3a-f in 25-40%
yield.
X
R1
R1
O
Alk
Alk
1
3
N
N
2
H
N
N
R
3
N
N
R
4
5
10
9
PPA
2
6
8
2
O
Alk(Ar)
R3
R
1
7
3
1
1
1
1
1
1
1
X = O, H
2
, S; 2 a R = H; b R = Me; c R = Ph; 3 a–d, g R = H, e R = Me, f R = Ph,
1
2
2
3
3
R = Ph; a, c–f R = Me, g R = H; a, b, e, f R = Ph, c R = p-BrC
6
4
H ,
3
3
d R = p-MeOC
6
H
4
, g R = H
_
*
*
______
For Communication 70 see [1].
2
Evidence of other aromatic heterocycles of this type is restricted to the 4,9- and 4,10-diazapyrenes, e.g.
[
4-10].
_
_________________________________________________________________________________________
1
2
Stavropol State University, Stavropol 355009, Russia; e-mail: nauka@stavsu.ru. Rostov State
University, Rostov-on-Don 344090, Russia; e-mail: pozharsk@pozhar.rnd.runnet.ru. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No 8, pp. 1109-1114, August, 2002. Original article submitted December 28,
2
000.
9
68
0009-3122/02/3808-0968$27.00©2002 Plenum Publishing Corporation

Compound 3d was prepared from perimidine both by the action of p-methoxybenzalacetophenone and
of benzal-p-methoxyacetophenone under the same conditions. During the course of the reaction of the
α,β-unsaturated ketones, and possibly also the intermediate materials, they are partially polymerized to give oily
products. Attempts to increase the yield of the target substance by an increase in the molar ratio of starting
chalcone or by an increase in temperature gave more tarring and did not lead to the desired result. We believe
that the initial stage of the reaction is an electrophilic C-alkylation by the chalcone at the 6(7) position of the
corresponding perimidine (Scheme 1). Subsequent intramolecular hydroxyalkylation and dehydration of the
ketones 4 then gives the dihydrodiazapyrene 5 which spontaneously oxidizes to 3 (compare with the ready
autooxidation of dihydro-1,3,6,8-tetraazapyrene derivatives [12, 13]).
Scheme 1
R1
R1
N
NH
N
NH
+
2
3
H
[O]
–H O
R CH=CHCOR
3
2
H O
2
+
2
H
R3
R2
R2
R3
O
4
5
Unfortunately, confirmation of this sequence of stages proved difficult since, even when carrying out
the reaction at room temperature (7 days; yield of 3a 51%) no kind of intermediate product could be detected.
None the less, an indirect reason to support Scheme 2 is the fact that p-nitrobenzalacetophenone (which is much
less basic than the unsubstituted chalcone) does not participate in this reaction. This indicates that the rate
limiting stage of the process is the first step. We have further shown that the formation of diazapyrenes is also
catalyzed by 60% perchloric acid, but due to more extensive tarring the product yield is significantly less in this
case. The ease of oxidative aromatization of the intermediates 5 points to the high thermodynamic stability of
the 1,3-diazapyrene system.
We expected to obtain analogs of the intermediate products 5 by the alkylation of perimidine by
1
2
1
β,β-disubstituted, unsaturated ketones of the type R R C=CHCOR but in this case the aromatization is not
1
2
possible. However, with dypnone (R = Ph, R = Me) the reaction does not occur, even when heated above
1
2
1
00°C and in the case of mesityl oxide (R = R = Me) complete tarring is observed.
The unsubstituted 1,3-diazapyrene 3g can be prepared similarly to phenalenone [14] by the reaction of
perimidine with glycerol at 138°C in 70% H
2
SO in the presence of sodium m-nitrobenzenesulfonate as oxidant.
4
However, in preparative mode, it is more convenient to use the system glycerol–PPA at 180-190°C without
oxidant (the use of the latter has no effect on the 27% yield). Basically, this is the reaction of perimidine with
acrolein in situ.
β-Diketones prove to be a good synthon for the preparation of 1,3-diazapyrenes from perimidine. In the
example of acetylacetone the reaction in PPA is initiated only above 100°C but the sole product (in 10% yield)
is the rather unexpected 4(9)-acetylperimidine (7). Evidently, this is the result of a retroaldol condensation of
intermediate 6 (Scheme 2). Introduction of an electrophile at position 4 can account for the repeated observation
of isomerization of the initially formed 6(7)-acylation product to the 4(9) isomer [15].
9
69

TABLE 1. Spectroscopic Parameters for Compound 3
1H NMR spectrum, δ, ppm, (J), Hz*
Com-
pound
2
H, s
4H, d
10H, d
5H, d
9H, d
8.49
7H
R1
R2
R3
3
3
a
b
9.81
9.76
8.74 (J = 9.14)
8.26 (J = 9.14)
8.20, s
8.14, s
—
—
7.58-7.66, m
7.40-7.75, m
8.77
8.98
8.32
3.19, s
7.62, s
(
(
(
J = 9.39)
(J = 9.39)
(J = 9.39)
(J = 9.39)
3
3
3
3
c
d
e
f
9.79
9.66
_
8.62
8.68
8.21
8.22
8.10, s
8.08-8.11, m
8.10, s
—
J = 9.43)
(J = 9.43)
(J = 9.43)
(J = 9.43)
2
8.53
8.57
8.08-8.11, m
—
3.88 (s, CH3O); 7.17 (m-H* , d, J = 7.80,
2
J = 9.98)
(J = 10.65)
C6H4); 7.64 (o-H* , m, C6H4 and C6H5)
8.64
8.12
3.12, s
7.50-7.68, m
7.49-7.69, m
(
J = 9.44)
(J = 9.44)
_
8.60
8.20
8.09, s
8.80 (dd, J = 8.31 (o-m),
2
(
J = 9.47)
(J = 9.47)
J = 1.4 (o-p) o-H)* ;
2
7
.49-7.69 (m, m- and p-H* )
3
g*3
9.75
8.70
8.24
8.27
—
—
(
J = 8.39)
(J = 8.39)
(t, J = 7.69)
_
*
*
*
______
Solvent: CDCl
3
(3a-c,e,f), DMSO-d
6
(3d), and CD CN (3g).
3
2
o-, m-, and p-H relative to the 1,3-diazapyrene ring.
δ, ppm (J, Hz): 8.58 (6H, 8H, d, J = 7.69).
3

Scheme 2
H
N
N
N
O
PPA
O
O
1
+
N
– MeCOMe
1
R = H
H
O
H
7
O
6
The synthesized 1,3-diazapyrenes are slightly yellowish, crystalline materials with a violet or blue
fluorescence under UV light. They readily dissolve in conc. HCl but the hydrochloride is hydrolyzed upon
dilution with water to yield the base as a precipitate. Quantum-chemical calculations (Fig. 1) point to a
significant π-deficiency in the molecule 3g while the change in effective charge on the hydrogen atoms matches
1
the position of their signals in the H NMR spectrum (see Table 1).
Overall, the signals of all of the protons of the diazapyrene ring are shifted to low field and appear at
δ > 8 ppm. The lowest field signal is that of the H-2 proton (δ 9.7-9.8 ppm) and the highest are those of the
H-5(9) and H-7 protons (δ 8.10-8.27). The increased anisotropy close to the conjugated ring [16] accounts for
the fact that the 6-CH
position 2 in compound 3e (δ 3.19 and 3.12 ppm respectively).
As expected, the IR spectra of compounds 3 show the presence of the stretching vibrations of the
3
group of compound 3b appears to lower field than the CH
3
group in the electron deficient
-1
aromatic ring (1620-1500 cm ) and the absence of any other characteristic absorption bands.
The high intensity of the molecule ion peak (100%) in the mass spectrum of 3b indicates, in our view,
the stability of the cation radical derived from the 1,3-diazapyrene. Besides the [M+1] signal with the correct
calculated intensity, the spectrum shows (in particular) peaks for [M-15] and [M-77] corresponding to the loss
of methyl or phenyl radicals.
Fig. 1. Effective charges on the atoms in 1,3-diazapyrene (ab initio method).
EXPERIMENTAL
1
H NMR spectra were recorded on a Bruker WP-200 (200 MHz) instrument using TMS as internal
standard and signal assignments were carried out using the double resonance method. IR Spectra were taken on
a UR-20 spectrometer and mass spectra on an MX-1321A instrument. Monitoring of the course of the reaction
9
71

and the purity of the synthesized compounds was carried out on Silufol UV-254 plates. The column
chromatography was performed using L40/100 silica gel from the supplier Chemapol.
General Method for the Synthesis of 1,3-Diazapyrene Derivatives 3. A mixture of perimidine or
-R-perimidine (0.002 mol), the corresponding chalcone (0.003 mol) and PPA (4 g) was stirred for 3 h at
0-65°C and then poured as a thin stream into water (100 ml) with vigorous stirring. After basification to pH ~ 8
2
6
with aqueous ammonia the precipitate was filtered off, washed with water, and dried. It was then extracted with
refluxing benzene (3 × 10 ml), cooled, and transferred to a silic gel chromatographic column where it was
initially eluted with benzene and then with ethyl acetate. The first fraction contained a small amount of oily
material and was not used. Evaporation of solvent from the second fraction gave the corresponding
1
,3-diazapyrene.
,8-Diphenyl-1,3-diazapyrene (3a). Yield 0.26 g (36%) (from benzalacetophenone). Pale yellow
crystals with mp 175-176°C (from octane; revision from the data in [11]). Found, %: C 87.49; H 4.64; N 7.92.
. Calculated, %: C 87.62; H 4.52; N 7.86.
6
C
H
26 16
N
2
6
-Methyl-8-phenyl-1,3-diazapyrene (3b). Yield 0.17 g (29%) (from benzalacetone). Pale yellow
-1
crystals with mp 198-199°C (benzene). IR spectrum (vaseline oil), ν, cm : 1620, 1595, 1568 (ring). Mass
+
spectrum, m/z (I, %): 294 [M ] (100), 295 (23), 279 (24), 217 (7). Found, %: C 85.65; H 4.89; N 9.79. C21
H
14
N .
2
Calculated, %: 85.69; H 4.79; N 9.52.
8
-p-Bromophenyl-6-phenyl-1,3-diazapyrene (3c). Yield 0.28 g (32%) (from p-bromobenzal-
acetophenone). Pale cream crystals with mp 216-217°C (ethyl acetate). Found, %: C 71.59; H 3.44; N 6.62.
. Calculated, %: C 71.74; H 3.47; N 6.44.
C
26
H
15BrN
2
8
-p-Methoxyphenyl-6-phenyl-1,3-diazapyrenene (3d). Yield 0.31 g (40%) (p-methoxybenzal-
acetophenone) and 0.22 g (28%) (from benzal-p-methoxyacetophenone). Pale yellow crystals with
mp 160-161°C (benzene–petroleum ether). Samples obtained by the two methods did not give a depression of
melting point. Found, %: C 83.84; H 4.74; N 7.39. C27
H
18
N O. Calculated, %: C 83.94; H 4.66; N 7.25.
2
2
-Methyl-6,8-diphenyl-1,3-diazapyrene (3e). Yield 0.20 g (27%) (from 2-methylperimidine and
benzalacetophenone). Pale yellow crystals with mp 182-183°C (benzene–hexane). Found, %: C 87.67; H 5.09;
N 7.64. C27 . Calculated, %: C 87.54; H 4.90; N 7.56.
,6,8-Triphenyl-1,3-diazapyrene (3f). Yield 0.22 g (25%) (from 2-phenylperimidine and benzal-
H
18
N
2
2
-1
acetophenone). Yellowish crystals with mp 267-268°C (benzene–hexane). IR Spectrum (vaseline oil), ν, cm :
618, 1593, 1568 (ring). Found, %: C 88.96; H 4.80; N 6.36. C32 . Calculated, %: C 88.86; H 4.66; N 6.48.
,3-Diazapyrene (3g). A. Condensation in H SO . Perimidine (6.72 g, 0.04 mol), ferrous sulfate
1.74 g), and glycerol (10.4 g, 0.11 mol) were mixed with 70% H SO (100 g) and the mixture was heated to
10°C. Over the course of 15 min, sodium m-nitrobenzenesulfonate (3 g, 0.013 mol) was added. The mixture
1
H
20
N
2
1
2
4
(
1
2
4
was heated to 138°C, held for 40 min, and then cooled to room temperature. The solution was filtered through a
glass filter and the filtrate was poured into a mixture of NaOH (40%, 150 ml) and ice (150 g). The precipitate
was filtered off, washed with water, and dried. The product was extracted with refluxing octane (5 × 50 ml)
which after evaporation gave compound 3g (3.23 g, 40%) as pale yellow crystals with mp 178-180°C (octane).
Found, %: C 82.48; H 4.03; N 13.60. C14
H
8
2
N . Calculated, %: C 82.34; H 3.95; N 13.72.
B. Condensation in PPA. Glycerol (2 g, 0.022 mol, previously dried by heating at 170°C) was added
dropwise over 15-20 min with stirring into to a mixture of perimidine (0.34 g, 0.002 mol) and PPA (5 g) which
had been heated to 190°C. After 1.5 h the mixture was cooled to 70°C and poured into ground ice (75 g). It was
then basified with ammonia solution to pH ~ 8 and extracted with ethyl acetate (3 × 50 ml). The solution
evaporated to 30 ml was chromatographed through a small amount of silica gel, washing the product with ethyl
acetate. Evaporation of solvent gave 1,3-diazapyrene (0.12 g, 29%).
Reaction of Perimidine with Ethyl Acetate in PPA. A mixture of perimidine (0.34 g, 0.002 mol),
acetylacetone (0.3 g, 0.003 mol), and PPA (4 g) was stirred for 1.5 h at 120-130°C. After cooling to 80-85°C the
mixture was poured with vigorous stirring into cold water (100 ml), basified with aqueous ammonia to pH ~ 8,
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72

extracted with ethyl acetate (3 × 10 ml), the solution dried and purified by refluxing with silica gel and then the
solvent was evaporated. After crystallization from benzene, the 4(9)-acetylperimidine 7 (0.04 g, 10%) was
obtained with mp 201-202°C, agreeing with the corresponding data [15]. The IR spectrum was identical to that
of a known sample of compound 7.
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