Pyrimidines as Surrogates for 1,3-Dicarbonyl Compounds in peri Annulation of Perimidines en Route to 1,3-Diazapyrenes

Article abstract of DOI:10.1002/ejoc.201601589

A highly efficient protocol for acid-mediated peri annulation of perimidines with pyrimidines has been developed. Pyrimidines, used as surrogates for 1,3-dicarbonyl compounds, furnish benzo[gh]perimidines, which includes hardly available analogues, non-substituted, or mono-substituted at C-6, C-8. Limitations of reactions that use 5-bromopyrimidines are investigated.

Full text of DOI:10.1002/ejoc.201601589

A Journal of
Accepted Article
Title: Pyrimidines as surrogates for 1,3-dicarbonyl compounds in peri-
annulation of perimidines en route to 1,3-diazapyrenes
Authors: Alexander V Aksenov, Stanislav V Shcherbakov, Irina V
Lobach, Inna V Aksenova, and Michael Rubin
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601589
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601589
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10.1002/ejoc.201601589
European Journal of Organic Chemistry
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Pyrimidines as surrogates for 1,3-dicarbonyl compounds in peri-
annulation of perimidines en route to 1,3-diazapyrenes
Alexander V. Aksenov,*[a] Stanisvlav V. Shcherbakov,[a,b] Irina V. Lobach,[a]
Inna V. Aksenova,[a] and Michael Rubin*[a,c]
Abstract:
A highly efficient protocol for acid-mediated peri-
highly promising structure in molecular electronics, which
can be primarily attributed to the lack of synthetic methods
providing azapyrene subunits suitable for controlled oligo-
and polymerization. Herein we wish to report our synthetic
studies in this direction.
annulation of perimidines with pyrimidines was developed.
Pyrimidines, used as surrogates for 1,3-dicarbonyl compounds allow
for furnishing benzo[gh]perimidines, including hardly available
analogs, non-substituted, or mono-substituted at C-6, C-8.
Limitations of reactions employing 5-bromopyrimidines are
investigated.
Me
N
R1
+
N
N
N
Introduction
A
N
2
3
R1
NH
R2,R3 = H
Organic poly-conjugated materials (molecular wires) are
widely used for the construction of conductive scaffolds for
molecular electronics. 1 Typically the architecture of a
molecular wire is designed as a linear polymer of rigidified
aromatic subunits, forming an extended π-system suitable
for efficient transfer of electrical charge. In addition, such
subunits should be amenable to routine modifications
attenuating their electronic and/or spectral properties, which
would allow for conversion of this simple building block into
N
B
COMe
COMe
R1
EtO
+
R2 = H
R3 = Me
5
N
N
4
R2
N
R2
O
C
N
N
R3
+
+
4
Me
+
R2
R3
R2
3
6
1
D
COCl
a
centerpiece of a semiconducting or photo-sensing
4
Ph
R2,R3 = H
7
molecular device. Currently, there is a growing interest in
aza-analogs of pyrenes possessing unusually low redox
potential and favorable structural features of their crystalline
lattice. Due to these unique properties, azapyrenes are
considered as highly promising materials for the
manufacture of organic semiconductor devices, c.a. light-
emitting diodes, field-effect transistors, and photo-voltaic
elements for solar cells. 2 In addition, such molecules
attracted attention as potential DNA-intercalators,3 a basis
for construction of molecular machines, 4 and for their
applications in coordination and supramolecular chemistry.5
However, there are no examples of application of these
E
O
+
4
R2
R3
8
Scheme 1.Synthetic approaches towards 1,3-diazapyrenes.
Results and Discussion
Several methods for preparation of 1,3-diazapyrenes (1) have
been reported, which include reactions of benzo[f]quinazolines 2
with activated methylideneoxonium equivalents, such as 1,3,5-
triazines 3 or DMF dimethylacetal6 (path A); condensations of
perimidines 4 with ethoxymethylene-1,3-dicarbonyl compounds
57 (path B); three-component couplings of perimidine 4 with
[a]
A. V. Aksenov, S. V. Shcherbakov, I. V. Lobach, I. V. Aksenova
Department of Chemistry
North Caucasus Federal University
1a Pushkin St., Stavropol 355009, RussianFederation
E-mail: alexaks05@rambler.ru
Department of Organic Chemistry
People’sFriendship University ofRussia
6 Miklukho-Maklaya St., Moscow, 117198, RussianFederation
M. Rubin
Department of Chemistry
University of Kansas
1251 Wescoe Hall Dr., Lawrence, KS 66045-7582, USA
E-mail: mrubin@ku.edu
1,3,5-triazines
3 and enol ethers or enolizable carbonyl
compounds 68 (path C); electrophilic acylations of perimidines 4
with cynnamoyl chlorides 7 accompanied by the cleavage of an
[b]
[c]
9
aromatic group (path D); or oxidative condensations of
perimidines 4 with chalchones 810 or cinnamic acids11 (path E)
(Scheme 1). Most of these processes, however, are highly sub-
strate-specific and provide, in the general case, only marginal
results. Much more appealing seems the straightforward and
general approach recently developed in our group utilizing an
acid-mediated reaction between 1H-perimidines 4 and various
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10.1002/ejoc.201601589
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protocol reported by Borovlev utilizing acroleine or glycerol
allowed for preparation of such compounds providing, however,
unacceptably low yields.10a Also, in our attempts to incorporate
a halogen at C-7 of 1,3-diazopyrene, we attempted acid-assisted
reactions of 4 (R1 = Ph) with 3-bromopentane-2,4-dione (10).
This reaction, however, did not provide any target product 11
(Scheme 2). Apparently, these more fragile 1,3-dicarbonyl
compounds appeared incompatible with the relatively harsh
reaction conditions necessary for peri-annulation of perimidines.
We wondered if pyrimidines could be employed as masked
1,3-dicarbonyl compounds in this type of transformation. Indeed,
although ANRORC-type formal 3+3 ring closures involving a C3-
unit originated from pyrimidines are quite rare, they are still
possible.13 We envisioned that under acidic conditions pyrimid-
ine would give highly electrophilic protonated form 12 further
participating in an SEAr-type reaction with perimidine 4 (Scheme
3). Such alkylation would involve the most electron rich atom C-
6(8) to provide intermediate 13, existing in the equilibrium with
form 14, which possesses a protonated sp3-hybridized nitrogen
N
R1
N
R1
O
O
R2
N
70% H2SO4
NH
+
R2
R3
R2 = Alk, Ar, H;
R3 = Alk, Ar
1
9
4
R3
Br
N
Ph
Me
Me
Me
10
X
N
O
O
Br
70% H2SO4
R1 = Ph
11
Me
Scheme 2.Employment of 1,3-dicarbonyl compounds for peri-annulation of
perimidines.
N
R1
NH
N
R1
R2
N
PPA
NH
+
NH
NH
atom in the 1,6-dihydropyrimidine moiety.
The latter could
N
12
4
13
R3
R3
serve as a good leaving group, triggering a ring-opening process
to yield intermediate 15. Finally, an intramolecular SEAr reaction
would occur accompanied by elimination of formamidine, to
furnish aminomethaniminium ion 16, which after deprotonation
would afford the desired 1,3-diazapyrene 1 (Scheme 3). In
order to test this idea, we stirred a mixture of perimidine (4a) and
pyrimidine (12a) (1.5 equiv.) in polyphosphoric acid (PPA, 86%)
for 5 hr at 250 oC.14 Although the process required forcing
conditions for completion, diazapyrene 1aa was isolated from
this mixture as the sole product, although in humble yield
(Scheme 4). Similar yields of diazapyrenes 1ba, 1ca, and 1fa
were obtained in reactions of 12a with substituted perimidines
4b, 4c, and 4f, respectively (Scheme 4). In spite of these
modest yields, for obtaining 1,3-diazapyrenes with non-sub-
stituted positions C-6 and C-8, the newly developed approach
proved superior to all alternative methods known to date.
Inspired by these results, we attempted to adapt this method-
ology to the synthesis of another challenging type of synthetic
target: diazapyrenes with a single substituent at C-6(8).
R2
~H
N
R1
N
R1
N
N
-H3PO4
H
NH2
R2
N
H
R3
H2N
NH R3
15
- HN=CH-NH2
R2
H2PO4
14
N
R1
N
R1
H2PO4
H
N
R2
N
R2
-H3PO4
1
16
R3
R3
Scheme 3. Proposed mechanistic rationale for peri-annulation of perimidines
To this end, the reactions of perimidines 4a-c were carried
out in the presence of 4-methyl- (12b) or 4-phenyl-1,3-pyrimidine
with pyrimidines.
1,3-diketones 9. This method affords good yields of 1,3-diaza-
pyrenes 1 substituted at C-6 and C-8 (Scheme 2), and proved
amenable to a double-fold peri-annulation of biperimidines en
route to the corresponding bis-diazapyrenes.12 However, to
prepare molecular wire subunits that can be linked in a chain (for
example, via appropriate transition metal-catalyzed cross-
coupling reactions), it was essential to gain access to 1,3-
diazapyrenes subunits that are not substituted at C-6 and C-8,
since steric hindrance of these substituents could suppress the
linking process. We previously demonstrated that the reaction
of 4 involving 1,3-ketoaldehydes (9, R2 = Ar, R3 = H) can be
carried out to afford the corresponding diazopyrenes with a
single substituent at C-6.12b However, attempts to employ
malonaldehyde (9, R2 = R3 = H) targeting diazopyrenes non-
substituted at both C-6 and C-8 proved unfruitful. An alternative
Figure 1.ORTEP drawing of 1ac (CCDC #1514188) showing atom labelling
scheme and 50% probability amplitude displacement ellipsoids.
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10.1002/ejoc.201601589
European Journal of Organic Chemistry
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R1
NH
N
R1
N
R1
N
R1
NH
N
86% PPA, 250 o
C
H+
N
N
Br
X
N
N
N
Br
12a
4a: R1 = H;
1aa: R1 = H, 32%;
1ba: R1 = Me, 30%;
1ca: R1 = Ph, 45%
17
18
4a: R1 = H;
4b: R1 = Me;
N
4b: R1 = Me;
4c: R1 = Ph
4f: R1 = 4-MeOC6H4
1fa: R1 = 4-HOC6H4, 57%
N
Me
H2SO4, 17
N
86% PPA, 250 o
C
N
R1
HO3S
R1= Me
R2
N
N
N
19b
R2
12b: R2 = Me;
12c: R2 = Ph
1ab: R1 = H, R2 = Me, 78%;
1ac: R1 = H, R2 = Ph, 75%;
1bc: R1 = Me, R2 = Ph, 85%;
1cc: R1 = Ph, R2 = Ph, 79%
N
R1
NH
N
R1
17
MeSO3H, RT
NH
H
N
4
Scheme 4. Preparation of 6,8-unsubstituted and 6(8)-monosubstituted 1,3-
diazapyrenes via peri-annulation of perimidines with pyrimidines.
N
20
Br
4a, 20a: R1 = H, 87%;
4e, 20e: R1 = 4-EtC6H4, 98%;
4f, 20f: R1 = 4-MeOC6H4, 98%
4g, 20g: R1 = 2-ClC6H4, 96%;
4b, 20b: R1 = Me, 85%;
4c, 20c: R1 = Ph, 95%;
4d, 20d: R1 = 4-ClC6H4, 98%;
R1
NH
N
R1
N
86% PPA, 250 o
C
4h, 20h: R1 = 4-(i-Pr)C6H4, 97%;
R2
N
N
N
Scheme 6. Attempted peri-annulation of perimidines with 5-bromopyrimidines.
R3
R2
R3
4a: R1 = H;
4b: R1 = Me;
4c: R1 = Ph
4d: R1= 4-ClC6H4
4e: R1= 4-EtC6H4
4f: R1= 4-MeOC6H4
12
1ad: R1 = H, R2 = R3 = Me, 73%;
1ae: R1 = H, R2 = R3 = Ph, 68%;
1bd: R1 = R2 = R3 = Me, 78%;
1be: R1 = Me, R2 = R3 = Ph, 65%;
1cd: R1 = Ph, R2 = R3 = Me, 82%;
1ce: R1 = R2 = R3 = Ph, 74%;
bromopyrimidine 17 did take place at room temperature in
methanesulfonic acid,16 leading to alkylation product 20a in
high yield. A series of perimidines with different substitu-
ents at C-2 (4b-h) also reacted smoothly affording the same
type of mono-alkylation products 20b-h (Scheme 6).
However, peri-annulation did not take place at all and the
diazapyrene scaffold was not formed under these reaction
1de: R1 = 4-ClC6H4, R2 = R3 = Ph, 80%;
1ee: R1 = 4-EtC6H4, R2 = R3 = Ph, 84%;
1fe: R1 = 4-MeOC6H4, R2 = R3 = Ph, 85%
12d: R2 = R3 = Me;
12e: R2 = R3 = Ph
conditions.
Evidently, the ANRORC process was
Scheme 5. Preparation of 6,8-disubstituted 1,3-diazapyrenes via peri-
suppressed in this case, probably due to the M+-donating
character of the halogen substituent, which caused
dissipation of positive charge in the reactive intermediate 14
(Scheme 3). Naturally, we decided to employ more forcing
conditions to promote the ring opening. To this end,
compound 20a was heated for 5 hr in 70% sulfuric acid at
180 oC. These attempts, however, did not result in the
formation of the targeted structure 18. We managed to
isolate from the reaction mixture a pentacyclic core of 7H-
imidazo[4',5':4,5]benzo[1,2,3-gh]perimidine (21a) along with
minor amounts of 1,3-diazapyrene (1aa) resulting from an
unexpected loss of a halogen atom (Scheme 7). An almost
identical result was obtained when a mixture of perimidine
annulation of perimidines with pyrimidines.
(12c). Gratifyingly, the corresponding peri-annulation products
1ab, 1ac, 1bc, 1cc were obtained in good yields (Scheme 4).
The structure of 1,3-azopyrene 1ac was unambiguously proved
by X-ray crystallography (Figure 1). Next, we reserved efforts to
test the generality and versatility of this approach, as well as its
amenability to assembling 1,3-diazopyrene scaffolds bearing two
substituents at C-6 and C-8. To this end, we carried out
reactions of perimidines 4a-f in the presence of 4,6-dimethyl-
(12d) and 4,6-diphenylpyrimidine (12e) to obtain variety of 1,3-
diazapyrenes in good to excellent yields (Scheme 5).
To address the issue with the synthesis of 7-bromo-
1,3-diazapyrenes 18, we attempted to perform an acid-
assisted reaction between perimidine (4a) and 5-bromo-
pyrimidine (17). It was discovered that reaction in sulfuric
acid with 2-methylperimidine (4b) afforded only sulfonation
product 19b,15 whereas formation of a new C-C bond did
not occur (Scheme 6). The SEAr process involving
o
(4a) and 5-bromopyrimidine (17) was heated at 140-150 C
in 86% PPA (optimization of this reaction is given in Table
1). This reactivity trend proved general, as for all tested
starting materials 20a-d, the corresponding imidazoles 21a-d
were obtained in marginal yields, accompanied by diaza-
pyrenes 1aa-1da, respectively (Scheme 7).
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10.1002/ejoc.201601589
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N
moiety at the peri-position of the perimidine ring followed by
deprotonation would afford pentacyclic core 29, which would
be further transformed into the fully aromatic poycyclic
product 21 via aerobic oxidation (Scheme 8). We also
rationalized that 1,3-diazapyrene 1 forming as a minor
product in this transformation could be obtained via the
plausible mechanism depicted in Scheme 9. Thus, we
reasoned that the intermediate allyl bromide 25 should exist
in equilibrium with iminium form 30, which can undergo
intramolecular nucleophilic attack with a lone pair of the
neighboring bromine atom to afford the reactive 2,5-dihydro-
1,3-bromazol-1-ium species 31. Deprotonation of this inter-
mediate at C-2 would trigger opening of the five-membered
ring to afford carbamimidic bromide 32 (Scheme 9).
Protonation of this molecule at N-1 of the perimidine
followed by tautomerization would provide stabilized
aminobromomethaniminium
N
N
N
NH
N
H2SO4
H
N
+
180 oC
HN
N
20a
Br
N
1aa: 20%
21a: 45%
N
R1
NH
Br
N
86% PPA
+
140-150 oC, 4-5 h
N
17
4a: R1 = H;
4b: R1 = Me;
4c: R1 = Ph;
N
R1
N
R1
N
N
+
HN
N
N
R1
NH
N
R1
NH
H
21a: R1 = H, 46%;
21b: R1 = Me, 41%;
21c: R1 = Ph, 35%
1aa: R1 = H, 21%;
1ba: R1 = Me, 25%;
1ca: R1 = Ph, 32%
Br
N
HN
+
H
N
N
Br
22
23
4
Scheme 7. Unexpected formation of imidazoles in PPA-promoted reaction of
perimidines with 5-bromopyrimidines.
R1
N
R1
N
H
Table 1. Optimization of reaction between compounds 4b and 17 in 86% PPA.
NH
NH
N
NH
Temperature, oC
(time, h)
Yield, %a
N
N
Br
Br
24
20
20b
68
57
40
32
-
1ba
-
-
23
20
25
-
21b
-
-
-
-
41
33
-
H
1
2
3
4
5
6
7
60 (4)
80 (3)
R1
NH
N
N
R1
100 (2)
120 (2)
150 (2)
180 (1)
200 (1)
-Br
-H+
[O]
NH
HN
H
HN
N
26
Br
25
-
-
N
-H+
-
aNMR yields determined by analysis of crude reaction mixture with p-xylene as
N
R1
NH
N
R1
NH
internal standard.
We suggest the following mechanistic rationales to
explain this unusual reactivity. It is believed, that formation
of alkylation product 20 involves Friedel-Crafts type electro-
philic attack of perimidine 4 with protonated pyrimidine
(species 22). Next, we imagine that the 1,6-dihydro-
pyrimidine moiety in 20 may undergo 6π-electron pericyclic
rearrangement, leading to the formation of alkenylbromide
24, which after protonation is expected to provide
allylbromide 25 (Scheme 8). Subsequent 5-exo-tet nucle-
ophilic attack by the imine moiety would lead to cyclization
of the imidazolium ring in 26, which is accompanied by
deprotonation of the proximal C-H bond to restore the
aromaticity of the perimidine system in 27. Next, intramol-
ecular electrophilic attack of the tethered imidazolium
HN
HN
H
28
27
N
N
R1
N
R1
NH
N
N
HN
HN
21
29
N
N
Scheme 8. Plausible mechanistic rationale, explaining the formation of 1,6-
dihydropyrimidines 20 in the reaction of perimidines with 5-bromopyrimidines
and their further rearrangement into of imidazoles 21.
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10.1002/ejoc.201601589
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species 33, which could serve as the electrophilic component in
the subsequent intramolecular SEAr-type peri-annulation of the
including structures, non-substituted, or mono-substituted at C-6,
C-8, which are difficult to synthesize by other methods. Also, in
attempt to access 7-halogenated 1,3-diazapyrene scaffolds, we
investigated reactions of perimidines 4 with 5-bromopyrimidines
17. These reactions, however, did not provide the expected
perimidine ring system.
The resulting tetracyclic core 34
undergoes re-aromatization after elimination of carbamimidic
bromide, which subsequently decomposes into HBr and
cyanamide (Scheme 9). These mechanistic rationales are
structures.
Instead, under milder reaction conditions we
supported by the following experimental facts.
Firstly,
obtained products of single-fold electrophilic alkylation, 1,6-
dihydropyrimidines 20. Under more forcing conditions, non-
chemoselective peri-annulation proceeded via an unusual
ANRORC pathway affording pentacyclic imidazole cores 21
along with diazapyrenes 1, obtained as minor products.
compound 20 submitted to reaction with 86% PPA (mode A)
under the same conditions provided the same products 21 and 1
forming with similar kinetic rates and in the same yields as in the
direct peri-annulation of 4 in the presence of 17 (mode B).
Secondly, although the chemoselectivity of this process depends
on reaction temperature (expectedly, the ratio of products 21:1
becomes lower at elevated temperatures), it does not depend on
the mode of the reaction. These facts are evidence that
molecule 20 is generated in the reaction course as an
intermediate, further participating in the peri-annulation. We
also succeeded in detecting cyanamide forming in the mixture
as a by-product by GC (Scheme 9).
Experimental Section
Benzo[gh]perimidine (1aa,6 Typical procedure): A mixture of 1H-perim-
idine (168 mg, 1.00 mmol), pyrimidine (120 mg, 1.50 mmol), and 86%
PPA (4.0 g) was vigorously stirred at 250 oC for 4-5 hr. Then, the mixture
was cooled down to ~80 oC, poured into cold water (30 mL), and
neutralized with aqueous ammonia to pH ~7-8. Formed solid precipitate
was filtered out and re-crystallized from EtOAc to obtain the titled
compound as off-white crystals, yield 66 mg (0.32 mmol, 81%), mp 178-
1
180°C (EtOAc); H NMR (400 MHz, aceton-d6) δ 8.30 (t, J = 7.7 Hz, 1H,
N
R1
NH
N
R1
7-H), 8.46 (d, J = 9.1 Hz, 2H, 5,9-H), 8.56 (d, J = 7.7 Hz, 2H, 6,8-H), 8.70
(d, J = 9.1 Hz, 2H, 4,10-H), 9.76 (s,1H, 2-H); HRMS (TOF-ES): Calcd. for
C14H9N2 (M+H)+ 205.0760, Found 205.0765 (2.4 ppm).
N
~H+
Br
Br
2-Methylbenzo[gh]perimidine (1ba):17 light-brown crystals, mp 180-
180.5 °C (EtOAc); 1H NMR (400 MHz, aceton-d6) 1H NMR (400 MHz,
aceton-d6) δ 3.21 (s, 3H, Me), 8.21 (t, J = 7.7 Hz,1H, 7-H), 8.27 (d, J =
8.9 Hz, 2H, 5,9-H), 8.48 (d, J = 7.7 Hz, 2H, 6,8-H), 8.62 (d, J = 8.9 Hz,
2H, 4,10-H)ppm;
219.0917, Found 219.0919 (0.9 ppm).
30
N
N
25
NH
NH2
R1
HRMS (TOF-ES): Calcd. for C15H11N2 (M+H)+
N
N
R1
N
H
N
2-Phenylbenzo[gh]perimidine (1ca):6 light-brown crystals, mp 224-
226°C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.60 – 7.52 (m, 3H, 3,4,5-
H, 2-Ph), 8.07 (t, J = 7.7 Hz, 1H, 7-H), 8.23 (d, J = 9.2 Hz, 2H, 4,5-H),
8.34 (d, J = 7.7 Hz, 2H, 6,8-H), 8.47 (d, J = 9.2 Hz, 2H, 9,10-H), 8.81 (d,
J = 8.6 Hz, 2H, 2,6-H 2-Ph); 13C NMR (101 MHz, CDCl3) δ 114.8, 122.5,
127.1(2C), 127.6(2C), 128.8(2C), 128.9(2C), 129.0(2C), 129.6, 130.5,
135.9(2C), 139.3, 154.3(2C), 162.2; HRMS (TOF-ES): Calcd. for
C20H13N2 (M+H)+ 281.1073, Found 281.1074 (0.4 ppm).
Br
NH2
N
Br
N
32
31
H
NH2
R1
N
R1
NH
N
R1
N
N
N
4-(Benzo[gh]perimidin-2-yl)phenol (1fa): yellow crystals, mp 232-
233 °C (EtOAc); 1H NMR (400 MHz, DMSO-d6) δ 6.99 (d, J = 8.7 Hz, 2H,
3,5-H 2-Ph), 8.23 (m, 3H, 4,5,7-H), 8.63 (m, 4H, 6,8-H, 2,4-H 2-Ph), 8.75
(d, J = 9.2 Hz, 2H, 9,10-H), 10.00 (s, 1H, -OH); 13C NMR (101 MHz,
DMSO-d6) δ = 113.5, 115.5(2C), 121.7, 126.9(2C), 127.4, 128.8(2C),
129.3, 129.4(2C), 130.2(2C), 136.5(2C), 153.6(2C), 160.1, 161.1; IR
(NaCl, cm-1): 3213, 3037, 29526, 2349; HRMS (TOF-ES): Calcd. for
C20H13N2O (M+H): 297.1022, Found 297.1025 (1.0 ppm).
-H+
-HBr
-NH2CN
N
Br
NH2
N
Br
NH2
1
33
34
Scheme 9. Plausible mechanistic rationale, explaining the formation of 1,3-
diazapyrene 1 as a side product in the reaction of perimidines with 5-
bromopyrimidines.
6-Methylbenzo[gh]perimidine (1ab):8a off-white crystals, mp 178-180°C
(EtOAc); 1H NMR (400 MHz, CDCl3) δ 2.96 (s, 3H, Me), 7.86 (d, J =7.8
Hz, 1H, 7-H), 8.03 (d, J = 9.1 Hz, 1H, 9-H), 8.08 (d, J = 9.4Hz, 1H, 5-H),
8.16 (d, J = 7.8 Hz, 1H,8-H), 8.34 (d, J = 9.1 Hz 1H, 10-H), 8.56 (d, J =
9.4 Hz, 1H, 4-H), 9.71 (s, 1H, 2-H); 13C NMR (101 MHz, CDCl3) δ 19.6,
116.2 122.2, 125.9, 126.4, 127.7, 128.0, 129.0, 129.4, 132.4, 136.2,
137.7, 153.1, 153.7, 155.9; HRMS (TOF-ES): Calcd. for C15H11N2
(M+H)+ 219.0917, Found 219.0920 (1.3 ppm).
Conclusions
In conclusion, we developed a new general protocol for acid-
mediated peri-annulation of perimidines 4 with pyrimidines 12,
allowing for the efficient preparation of benzo[gh]perimidines 1,
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10.1002/ejoc.201601589
European Journal of Organic Chemistry
FULL PAPER
6-Phenylbenzo[gh]perimidine (1ac):8c,d off-white crystals, mp 176-
178 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.63 – 7.52 (m, 5H, Ph),
8.24 – 8.13 (m, 3H, 5,7,9-H), 8.45 (d, J = 8.0 Hz, 1H, 8-H), 8.55 (d, J =
9.1 Hz, 1H, 4-H), 8.64 (d, J = 9.6 Hz, 1H, 10-H), 9.79 (s, 1H, 2-H); 13C
NMR (101 MHz, CDCl3) δ 116.5, 122.7, 127.0, 127.1, 127.1, 128.2,
128.8 (2C), 128.9, 129.0, 129.2, 130.8 (2C), 134.6, 136.2, 139.6, 142.6,
153.4, 153.9, 156.2; IR (NaCl, cm-1): 3188, 3027, 2866, 2356; HRMS
(TOF-ES): Calcd. for C20H13N2 (M+H)+ 281.1073, Found 281.1074 (0.4
ppm).
J = 9.4 Hz, 2H, 5,9-H),8.69 (d, J = 9.4 Hz, 2H, 4,10-H),8.82 (d, J = 8.4 Hz,
2H, 2,6-H 2-Ph); 13C NMR (101 MHz, CDCl3) δ 19.6(2С), 115.3, 123.3,
126.1(2С), 126.7(2С), 128.8(2С), 129.0(2С), 130.4, 131.5, 132.5(2С),
137.5(2С), 139.4, 154.3(2С), 161.9; IR (NaCl, cm-1): 2959, 2925, 2855,
2349; HRMS (TOF-ES): Calcd. for C22H17N2 (M+H)+ 309.1386, Found
309.1389 (0.9 ppm).
2,6,8-Triphenylbenzo[gh]perimidine (1ce):8a yellow crystals, mp 267-
268 °C (CH2Cl2/acetone); 1H NMR (400 MHz, CDCl3) δ 7.69 – 7.53 (m,
13H, 6-Ph, 8-Ph, 3,4,5-H 2-Ph), 8.11 (s,1H, 7-H), 8.24 (d, J = 9.5 Hz, 2H,
5,9-H), 8.65 (d, J = 9.5 Hz, 2H, 4,10-H), 8.83 (d, J = 9.31 Hz, 2H, 2,6-H
2-Ph); 13C NMR (101 MHz, CDCl3) δ 115.5, 123.7, 126.5(2С), 127.5(2С),
128.2(2С), 128.7(4С), 128.8(2С), 129.1(2С), 130.4, 130.5, 130.9(4С),
134.3(2С), 139.2, 139.7(2С), 142.0(2С), 154.4(2С), 162.3; HRMS (TOF-
ES): Calcd. for C32H21N2 (M+H)+ 433.1699, Found 433.1699 (0.0 ppm).
2-Methyl-6-phenylbenzo[gh]perimidine (1bc): light-brown crystals, mp
186-188 °C (EtOAc); 1H NMR (400 MHz, DMSO-d6) δ 3.03 (s, 3H, Me),
7.74 – 7.55 (m, 5H 2-Ph), 8.28 – 8.08 (m, 3H, 5,7,9-H), 8.59 (d, J = 9.5
Hz, 1H, 8-H),8.71 (d, J = 7.9 Hz, 1H, 4-H),8.81 (d, J = 9.2 Hz, 1H, 10-H);
13C NMR (101 MHz, DMSO-d6) δ 26.6, 113.5, 122.0, 125.9, 126.4, 126.8,
128.1, 128.3, 128.7(2C), 128.8, 129.3, 130.6 (2C), 133.9, 136.5, 139.0,
141.6, 153.0, 153.7, 165.0; IR (NaCl, cm-1): 3028, 2970, 2865, 2349;
HRMS (TOF-ES): Calcd. for C21H15N2 (M+H)+ 295.1230, Found 295.1238
(2.7ppm).
2-(4-Chlorophenyl)-6,8-diphenylbenzo[gh]perimidine (1de): colorless
crystals (CH2Cl2/acetone), decomposed at 254-274 °C without melting;
1H NMR (400 MHz, CDCl3) δ 7.69 – 7.55 (m, 12H, 6-Ph, 8-Ph, 3,5-H 2-
(4-сhlorophenyl)), 8.13 (s, 1H, 7-H), 8.24 (d, J = 9.4 Hz, 2H, 5,9-H), 8.68
(d, J = 9.4 Hz, 2H, 4,10-H), 8.80 (d, J = 8.4 Hz, 2H, 2,6-H 2-(4-
сhlorophenyl)); 13C NMR (101 MHz, CDCl3) δ 115.6, 123.7, 126.6(2С),
127.4(2С), 128.3(2С), 128.8(4С), 129.0(2С), 130.4(2С), 130.6,
130.9(4С), 134.5(2С), 136.8, 137.7, 139.6(2С), 142.2(2С), 154.5(2С),
161.3; IR (NaCl, cm-1): 3201, 3050, 2886, 2349; HRMS (TOF-ES):
Calcd. for C32H20N2Cl (M+H)+ 467.1310, Found 467.1309 (-0.2 ppm).
2,6-Diphenylbenzo[gh]perimidine (1cc): light-brown crystals, mp 233-
235 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.66 – 7.53 (m, 8H, 3,4,5-
H 2-Ph, 6-Ph), 8.10 (d, J = 7.9 Hz, 1H, 7-H), 8.23 (d, J = 9.5 Hz, 1H, 9-H),
8.29 (d, J = 9.2 Hz, 1H, 5-H), 8.42 (d, J = 7.9 Hz, 1H, 8-H), 8.54 (d, J =
9.2 Hz, 1H, 4-H), 8.63 (d, J = 9.5 Hz, 1H, 10-H), 8.83 (d, J = 7.1 Hz, 2H,
2,6-H, 2-Ph); 13C NMR (101 MHz, CDCl3) δ 115.2, 123.1, 127.1, 127.6,
127.7, 128.2, 128.7(3С), 128.8(3С), 129.0, 129.1(2С), 130.5, 130.8(2С),
134.3, 136.0, 139.3, 139.8, 142.3, 154.1, 154.7, 162.3; IR (NaCl, cm-1):
3188, 3041, 2873, 2349; HRMS (TOF-ES): Calcd. for C26H17N2 (M+H)+
357.1386, Found 357.1396 (2.8 ppm).
2-(4-Ethylphenyl)-6,8-diphenylbenzo[gh]perimidine (1ee): light-green
crystals, (CH2Cl2/acetone), decomposed at 233-243 °C without melting;
1H NMR (400 MHz, CDCl3) δ 1.33 (t, J = 7.6 Hz, 3H, –CH3 2-(4-ethyl-
phenyl)), 2.78 (q, J = 7.6 Hz, 2H, –CH2- 2-(4-ethylphenyl)), 7.43 (d, J =
8.1 Hz, 2H, 3,5-H 2-(4-ethylphenyl)), 7.69 – 7.53 (m, 10H, 6-Ph, 8-Ph),
8.10 (s, 1H, 7-H), 8.24 (d, J = 9.4 Hz, 2H, 5,9-H), 8.64 (d, J = 9.4 Hz, 2H,
4,10-H), 8.74 (d, J = 8.1 Hz, 2H, 2,6-H 2-(4-ethylphenyl)); 13C NMR (101
MHz, CDCl3) δ 15.7, 29.0, 115.4, 123.7, 126.5(2С), 127.5(2С), 128.2(2С),
128.4 (2С), 128.7 (4С), 129.1 (2С), 130.4, 130.9 (4С), 134.2 (2С), 136.7,
139.7 (2С), 141.9 (2С), 147.1, 154.5 (2С), 162.5; IR (NaCl, cm-1): 3188,
3044, 2874, 2348; HRMS (TOF-ES): Calcd. for C34H25N2 (M+H)+
461.2012, Found 461.2014 (0.4 ppm).
6,8-Dimethylbenzo[gh]perimidine (1ad):8a yellow crystals, mp 207-
209 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 2.98 (s, 6H, 6,8-Me), 7.74
(s, 1H, 7-H), 8.14 (d, J = 9.5Hz, 2H, 5,9-H), 8.73 (d, J = 9.5Hz, 2H, 4,10-
H), 9.65 (s, 1H, 2-H); HRMS (TOF-ES): Calcd. for C16H13N2 (M+H)+
233.1073, Found 233.1071 (0.9 ppm).
6,8-Diphenylbenzo[gh]perimidine (1ae):8a light-brown crystals, mp 175-
176 °C (CH2Cl2/acetone); 1HNMR (400 MHz, CDCl3) δ 7.65 – 7.50 (m,
10H, 6-Ph, 8-Ph), 8.15 – 8.13 (m, 3H, 5,7,9-H), 8.64 (d, J = 9.4 Hz, 2H,
4,10-H), 9.74 (s, 1H, H-2); 13C NMR (101 MHz, CDCl3) δ 116.8, 123.2,
126.4(2С), 126.8(2С), 128.2(2С), 128.7(4С), 130.7, 130.8(4С),
134.4(2С), 139.4(2С), 142.1(2С), 153.6(2С), 156.2; HRMS (TOF-ES):
Calcd. for C26H17N2 (M+H)+: 357.1386, Found 357.1396 (2.8 ppm).
2-(4-Methoxyphenyl)-6,8-diphenylbenzo[gh]perimidine(1fe):
yellow
crystals (CH2Cl2/acetone), decomposed at 288-305 °C without melting;
1H NMR (400 MHz, DMSO-d6) δ 3.89 (s, 3H, -OMe), 7.76 – 7.59 (m, 12H,
6,8-Ph, 3,5-H 2-(4-methoxyphenyl)), 8.10 (s, 1H, 7-H), 8.23 (d, J = 9.5 Hz,
2H,5,9-H), 8.59 (d, J = 9.5 Hz, 2H, 4,10-H), 8.72 (d, J = 8.8 Hz, 2H, 2,6-H
2-(4-methoxyphenyl)); 13C NMR (101 MHz, CDCl3, 25°C) δ 55.4, 114.2,
123.7, 125.5 (2С), 127.3 (2С), 127.9 (2С),128.3 (2С), 128.4, 128.8 (4С),
130.1 (2С), 130.7 (4С), 134.0 (2С), 134.9, 136.6, 138.7 (2С), 141.5 (2С),
153.7 (2С), 161.0; IR (NaCl, cm-1): 3199, 2929, 2858, 2349; HRMS
(TOF-ES): Calcd. for C33H23N2O (M+H)+ 463.1805, Found 463.1807 (0.4
ppm).
2,6,8-Trimethylbenzo[gh]perimidine (1bd):12a yellow-green crystals, mp
241-243 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 2.95 (s, 3H, 2-Me),
3.13(s, 6H, 6,8-Me), 7.71 (s, 1H, 7-H), 8.12 (d, J = 9.5 Hz, 2H, 5,9-H),
8.71 (d, J = 9.5 Hz, 2H, 4,10-H); HRMS (TOF-ES): Calcd. for C17H15N2
(M+H)+ 247.1230, Found 247.1233 (1.2 ppm).
2-Methyl-6,8-diphenylbenzo[gh]perimidine(1be):12a
light-brown
crystals, mp 182-183 °C (CH2Cl2/acetone); 1H NMR (400 MHz, CDCl3) δ
3.16 (s, 3H, 2-Me), 7.66 – 7.50 (m, 10H, 6-Ph, 8-Ph), 8.12 – 8.10 (m, 3H,
5,7,9-H), 8.63 (d, J = 9.4 Hz, 2H, 4,10-H); 13C NMR (101 MHz, CDCl3) δ
27.1, 114.7, 123.4, 126.2(2С), 126.6(2С), 128.2(2С), 128.7(2С), 130.3,
130.8(4С), 134.5(2С), 139.5(2С), 142.1(2С), 154.0(2С), 165.5; HRMS
(TOF-ES): Calcd. for C27H19N2 (M+H)+ 371.1543, Found 371.1545 (0.5
ppm).
2-Methyl-1H-perimidine-6-sulfonic acid (19b, Typical procedure): A
mixture of 2-methyl-1H-perimidine (182 mg, 1.00 mmol), 5-bromo-
pyrimidine (159 mg, 1.00 mmol), and 98% sulfuric acid (3 mL) was stirred
at room temperature for 1 hr. Then the mixture was poured into cold
water (50 mL), formed solid precipitate was filtered off and re-crystallized
from EtOAc to afford the titled compound as pale-yellow solid, yield 162
mg (0.62 mmol, 73%); decomposed at 290-340 °C without melting; 1H
NMR (400 MHz, DMSO-d6) δ 2.21 (s, 3H, 2-Me), 6.52 (d, J = 7.8 Hz, 1H),
6.60 (d, J = 7.3 Hz, 1H), 7.29 (t, J = 8.1 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H),
8.03 (d, J = 8.7 Hz, 1H); HRMS (TOF-ES): Calcd. for C12H10N2O3SNa
(M+Na)+ 285.0304, Found 285.0307 (1.05 ppm).
6,8-Dimethyl-2-phenylbenzo[gh]perimidine
(1cd):
yellow-green
crystals, mp 193-195 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 3.02 (s,
6H 6,8-Me), 7.62 – 7.52 (m, 3H, 3,4,5-H 2-Ph), 7.80 (s, 1H, 7-H), 8.23 (d,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601589
European Journal of Organic Chemistry
FULL PAPER
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-1H-perimidine (20a, Typical
procedure): A mixture of 1H-perimidine (168 mg, 1.00 mmol), 5-bromo-
pyrimidine (159 mg, 1.00 mmol) and methanesulfonic acid (15 mL) was
stirred at room temperature for 15 min. Then the mixture was poured
into cold water (50 mL), formed solid precipitate was filtered off and re-
crystallized from EtOAc to afford the titled compound as light-brown
crystals, yield 285 mg (0.87 mmol, 87%); decomposed at 186-188 °C
without melting; 1H NMR (400 MHz, aceton-d6) δ 5.74 (s, 1H, 4-H 6-pyr),
6.56-6.52 (m, 2H, 4,9-H), 6.77 (s, 1H, 6-H 6-pyr), 7.10 (s, 1H, 2-H 6-pyr),
7.19-7.24 (m, 2H, 7,8-H), 7.36 (s, 1H, 2-H), 7.49 (d, J = 8.6 Hz, 1H, 5-H);
13C NMR (101 MHz, DMSO-d6) δ 58.7, 100.5, 107.9(2С), 115.2, 123.2,
128.6(2С), 129.2, 130.8, 132.9, 141.6(2С), 144.2, 146.1; IR (NaCl, cm-1):
2870, 2780, 2352, 1615; HRMS (TOF-ES): Calcd. for C15H12BrN4
(M+H)+ 327.0240, Found 327.0237 (-0.9 ppm).
7.05 (d, J = 8.8 Hz, 2H, 3,5-H 2-(4-methoxyphenyl)), 7.13 (s, 1H, 2-H 6-
pyr), 7.28 – 7.23 (m, 2H, 7,8-H), 7.50 (d, J = 8.6 Hz, 1H, 5-H), 8.06 (d, J
= 8.8 Hz, 2H, 2,6-H 2-(4-methoxyphenyl)); 13C NMR (101 MHz, aceton-
d6) δ 55.5(2C), 105.2, 113.9, 114.1, 121.2, 122.8, 124.6, 126.0, 128.8
(4C), 129.6, 130.8, 132.6, 142.3(2C), 147.7, 152.5, 161.9; IR (NaCl,
cm-1): 3183, 3027, 2873, 2345, 1711; HRMS (TOF-ES): Calcd. for
C22H18BrN4O (M+H)+: 433.0659, Found 433.0660 (0.2 ppm).
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-(2-chlorophenyl)-1H-perim-
idine (20g): yellowish crystals (EtOAc), decomposed at 181-186°C
without melting; 1H NMR (400 MHz, aceton-d6) δ 5.78 (s, 1H, 4-H 6-pyr),
6.66 – 6.62 (m, 2H, 4,9-H), 6.77 (s, 1H, 6-H 6-pyr), 7.17 (s, 1H, 2-H 6-
pyr), 7.29 – 7.24 (m, 2H, 7,8-H), 7.54 – 7.44 (m, 4H, 3,4,5-H 2-(2-
chlorophenyl), 5-H), 7.68 (d, J = 8.8 Hz, 1H, 6-H 2-(2-chlorophenyl)); 13
C
NMR (101 MHz, DMSO-d6) δ 58.4, 101.0, 102.9, 115.8, 121.9, 127.4,
128.9(2С), 129.7, 130.0(2С), 130.4(2С), 131.2, 131.4, 132.8, 134.5,
138.6 (2С), 144.6, 152.7; IR (NaCl, cm-1): 2887, 2780, 2370, 1635;
HRMS (TOF-ES): Calcd. for C21H15BrClN4 (M+H)+: 437.0163, Found
437.0167 (0.9 ppm).
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-methyl-1H-perimidine (20b):
pale-yellow crystals (EtOAc), decomposed at 212-214 °C without melting;
1H NMR (400 MHz, aceton-d6) δ 2.08 (s, 3H, 2-Me), 5.76 (s, 1H, 4-H 6-
pyr), 6.54-6.50 (m, 2H, 4,9-H), 6.77 (s, 1H, 6-H 6-pyr), 7.24-7.15 (m, 3H,
7,8-H, 2-H 6-pyr), 7.46 (d, J= 8.6 Hz, 1H, 5-H); 13C NMR (101 MHz,
DMSO-d6) δ 21.2, 58.7, 100.8, 106.2(2С), 114.6, 121.4, 128.5(2С), 128.7,
132.7, 142.0(2С), 144.2, 153.9; IR (NaCl, cm-1): 2886, 2755, 2358, 1617;
HRMS (TOF-ES): Calcd. for C16H14BrN4 (M+H)+ 341.0396, Found
341.0400 (1.2 ppm).
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-(4-isopropylphenyl)-1H-per-
imidine (20h): yellowish crystals (EtOAc), decomposed at 175-179 °C
without melting; 1H NMR (400 MHz, aceton-d6, 25°C) δ 1.27 (s, 3H, -СH3
2-(4-isopropylphenyl)), 1.28 (s, 3H, -СH3 2-(4-isopropylphenyl)), 3.03-
2,94 (m, 1H, -CH- 2-(4-isopropylphenyl)), 5.80 (s, 1H, 4-H 6-pyr), 6.75 –
6.71 (m, 2H, 4,9-H), 6.79 (s, 1H, 6-H 6-pyr), 7.19 (s, 1H, 2-H 6-pyr), 7.29
– 7.24 (m, 2H, 7,8-H), 7.40 (d, J = 8.3 Hz, 2H, 3,5-H 2-Ph), 7.50 (d, J =
8.6 Hz, 1H, 5-H),8.02 (d, J = 8.3 Hz, 2H, 2,6-H 2-(4-isopropylphenyl));
13C NMR (101 MHz, aceton-d6) δ 24.1(2С), 34.8, 59.8, 102.4, 105.1,
109.6, 116.2, 123.1, 127.3 (2С), 127.7(2С), 129.5, 129.8, 130.1, 131.5,
132.3, 134.1, 143.0(2С), 145.0, 153.0, 153.1; IR (NaCl, cm-1):3212, 3018,
2869, 1715; HRMS (TOF-ES): Calcd. for C24H22BrN4 (M+H)+ 445.1022,
Found 445.1025 (0.7 ppm).
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-phenyl-1H-perimidine (20c):
pale-yellow crystals (EtOAc), decomposed at 174-180°C without melting;
1H NMR (400 MHz, aceton-d6, 25°C) δ 5.79 (s, 1H, 4-H 6-pyr), 6.78 –
6.72 (m, 3H, 4,9-H, 6-H 6-pyr), 7.17 (s, 1H, 2-H 6-pyr), 7.29 – 7.24 (m,
2H, 7,8-H), 7.57 – 7.49 (m, 4H, 3,4,5-H 2-Ph, 5-H), 8.08 (d, J=6.8 Hz, 2H,
2,6-H 2-Ph); 13C NMR (101 MHz, DMSO-d6) δ 58.4, 101.1, 103.3(2С),
115.1, 121.8, 126.9(2С), 128.4(2С), 128.9(2С), 130.1, 131.1(2С), 132.7,
133.2, 139.2(2С), 144.6, 152.4 ppm; IR (NaCl, cm-1): 2886, 2776, 2356,
1635; HRMS (TOF-ES): Calcd. for C21H16BrN4 (M+H)+: 403.0553,
Found 403.0557 (1 ppm).
Preparation
of
7H-Imidazo[4',5':4,5]benzo[1,2,3-gh]perimidines,
mode A (typical procedure): A mixture of 1H-perimidine (168 mg, 1.00
mmol), 5-bromopyrimidine (159 mg, 1.00 mmol), and 86% PPA(4 g) were
vigorously stirred 140–150 °С for 4-5 hr. Then, the mixture was cooled
down to ~80 oC, poured into cold water (30 mL), and neutralized with
aqueous ammonia to pH ~7-8. Formed solid precipitate was filtered out
and separated by preparative column chromatography on Silica gel
eluting with mixture EtOAc/EtOH 3:1 to obtain two fractions: 21a (0.25),
yield 112 mg (0.46 mmol, 46%) and 1aa (0.72), yield 43 mg (0.21 mmol,
21%).
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-(4-chlorophenyl)-1H-perim-
idine (20d): light-brown crystals (EtOAc), decomposed at 174-179°C
without melting; 1H NMR (400 MHz, aceton-d6) δ 5.80 (s, 1H, 4-H 6-pyr),
6.75-6.71 (m, 2H, 4,9-H), 6.79 (s, 1H, 6-H 6-pyr), 7.29-7.24 (m, 3H, 7,8-H,
2-H 6-pyr),7.56 – 7.50 (m, 3H, 3,5-H 2-(4-chlorophenyl), 5-H), 8.11 (d, J
= 8.6 Hz 2H, 2,6-H 2-(4-chlorophenyl));13CNMR (101 MHz, DMSO-d6) δ
58.6, 101.7, 104.3(2С), 115.8, 122.2, 129.0(2С), 129.2(2С), 130.0(2С),
132.4(2С), 133.1(2С), 136.3, 139.4(2С), 145.2, 151.9 ppm; IR (NaCl,
cm-1): 3076, 2887, 2340, 1630;
HRMS (TOF-ES): Calcd. for
C21H15BrClN4 (M+H)+: 437.0163, Found 437.0164 (0.2 ppm).
Preparation
of
7H-Imidazo[4',5':4,5]benzo[1,2,3-gh]perimidines,
mode B (typical procedure): 7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-1H-
perimidine (20a, 326 mg, 1.00 mmol) was dissolved in 70% sulphuric
acid and stirred at 180 oC for 4-5 hr. Then, the mixture was cooled down
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-(4-ethylphenyl)-1H-perim-
idine (20e): yellowish crystals (EtOAc), decomposed at 164-171°C
without melting; 1H NMR (400 MHz, aceton-d6) δ 1.25 (t, J = 7.6 Hz, 3H,
CH3 2-(4-ethylphenyl)), 2.72 (q, J = 7.6 Hz, 2H, -CH2- 2-(4-ethylphenyl)),
5.85 (s, 1H, 4-H 6-pyr), 6.77-6.73 (m, 2H, 4,9-H), 6.83 (s, 1H, 6-H 6-pyr ),
7.39-7.22 (m, 5H, 3,5-H 2-Ph, 7,8-H, 2-H 6-pyr),7.49 (d, J HH= 8.6 Hz,
1H, 5-H), 8.02 (d, J = 8.2 Hz, 2H, 2,6-H 2-(4-ethylphenyl)); 13C NMR
(101 MHz, DMSO-d6) δ 15.4, 28.1, 57.6, 102.0, 105.7, 114.8, 121.7,
126.9, 127.0(2С), 127.8(2С), 128.5, 129.0, 129.4, 130.6, 130.9, 132.7,
135.1(2С), 145.4, 147.3, 152.4; IR (NaCl, cm-1): 3180, 3026, 2348,
1596; HRMS (TOF-ES): Calcd. for C23H20BrN4 (M+H)+: 431.0866, Found
431.0864 (0.4 ppm).
o
to ~80 C, poured into cold water (30 mL), and neutralized with aqueous
ammonia to pH ~7-8. Formed solid precipitate was filtered out and
separated by preparative column chromatography on Silica gel eluting
with mixture EtOAc/EtOH 3:1 to obtain two fractions: 21a (0.25), yield
110 mg (0.45 mmol, 45%) and 1aa (0.72), yield 41 mg (0.20 mmol, 20%).
7H-Imidazo[4',5':4,5]benzo[1,2,3-gh]perimidine (21a): orange crystals
(EtOH), decomposed at 284-300°C without melting, 1H NMR (400 MHz,
DMSO-d6) δ 7.45 (br.s, 2H, 4,11-H), 8.50 (s, 1H, 2-H), 8.72 – 8.69 (m, 2H,
5,10-H), 9.31(s, 1H, 9-H), 9.77(s, 1H, 7-H); 13CNMR (101 MHz, DMSO-
d6) δ 107.3, 115.6, 118.4, 120.9, 126.8(2С), 127.5, 128.3(2С), 129.9,
139.6, 144.8, 148.9, 153.7, 155.9, 158.4; IR (NaCl, cm-1):3031, 2970,
2873, 2346; HRMS (TOF-ES): Calcd. for C15H7N4 (M-H)- 243.0676,
Found 243.0679 (1.2 ppm).
7-(5-Bromo-3,4-dihydropyrimidin-4-yl)-2-(4-methoxyphenyl)-1H-per-
imidine (20f): pale-yellow crystals (EtOAc), decomposed at 166-172°C
without melting; 1H NMR (400 MHz, Aceton-d6) δ 3.88 (s, 3H, OMe), 5.77
(s, 1H, 4-H 6-pyr), 6.73 – 6.69 (m, 2H, 4,9-H), 6.77 (s, 1H, 6-H 6-pyr),
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10.1002/ejoc.201601589
European Journal of Organic Chemistry
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2-Methyl-7H-imidazo[4',5':4,5]benzo[1,2,3-gh]perimidine (21b): dark
orange crystals (EtOH), decomposed at 297-315°C without melting, Rf
0.34 (EtOAc/EtOH 3:1); 1H NMR (400 MHz, DMSO-d6) δ 2.56 (s, 3H, 2-
Me), 7.32 – 7.30 (m, 3H, 4,11-H), 8.63 – 8.57 (m, 2H, 5,10-H), 8.50 (s,
1H, 9-H), 9.64 (s, 1H, 7-H); 13CNMR (101 MHz, DMSO-d6) δ 22.6, 109.8,
114.2, 118.5, 120.3, 126.6, 128.1(2С), 129.1(2С), 130.4, 141.7, 148.7,
153.5, 155.6, 158.6; IR (NaCl, cm-1):3063, 2954, 2873, 2399; HRMS
(TOF-ES): Calcd. for C16H9N4 (M-H)- 257.0833, Found 257.0837 (1.5
ppm).
[4]
[5]
V. Balzani, A. Credi, S. J. Langford, F. M. Raymo, J. F. Stoddart, M.
Venturi, J. Am. Chem. Soc. 2000, 122, 3542-3543.
(a) P. J. Stang, B. Olenyuk, J. Fan, A. M. Arif, Organometallics 1996,
15, 904-908; (b) P. J. Stang, D. H. Cao, S. Saito, A. M. Arif, J. Am.
Chem. Soc. 1995, 117, 6273-6283.
[6]
[7]
[8]
I. V. Aksenova, A. V. Aksenov, A. A. Zamorkin, V. I. Goncharov, Chem.
Heterocycl. Comp. 2008, 44, 197-199.
A. V. Aksenov, I. V. Borovlev, S. V. Pisarenko, I. V. Aksenova, Chem.
Heterocycl. Comp. 2008, 44, 868-871.
2-Phenyl-7H-imidazo[4',5':4,5]benzo[1,2,3-gh]perimidine (21c): dark
orange crystals (EtOH), decomposed at 305-317°C without melting, Rf
0.50 (EtOAc/EtOH 3:1); 1H NMR (400 MHz, DMSO-d6) δ 7.67 – 7.50 (m,
5H, 4,11-H, 3,4,5-H 2-Ph), 8.28 – 8.26 (m, 2H, 2,6-H 2-Ph), 8.71 – 8.67
(m, 2H, 5,10-H), 9.28 (m, 1H, 9-H), 9.72 (s, 1H, 7-H), 12.88 (br.s, 1H,
NH); 13CNMR (101 MHz, DMSO-d6) δ 109.4, 113.9, 118.6(2С), 121.6,
128.0, 128.8(3С), 129.3(3С), 129.9, 131.5, 134.0, 144.0(2С), 148.8,
153.7, 155.1, 158.2; IR (NaCl, cm-1): 3064, 2952, 2833, 2320; HRMS
(TOF-ES): Calcd. for C21H11N4 (M-H)- 319.0989, Found 319.0987 (0.6
ppm).
a) A. V. Aksenov, A. S. Lyahovnenko, I. V. Aksenova, O. N. Nadein,
Tetrahedron Lett. 2008, 49, 1808-1811; b) A. V. Aksenov, N. A.
Aksenov, N. S. Lyakhovnenko, A. B. Kumshaeva, I. V. Aksenova,
Chem. Heterocycl. Comp. 2012, 48, 634-641; c) A. V. Aksenov, I. V.
Aksenova, A. S. Lyakhovnenko, N. A. Aksenov, Chem. Heterocycl.
Comp. 2008, 44, 1379-1383; d) A. V. Aksenov, A. S. Lyakhovnenko, I.
V. Aksenova, N. A. Aksenov, Chem. Heterocycl. Comp. 2008, 44,
1291-1292.
[9]
a) O. P. Demidov, I. V. Borovlev, A. F. Pozharskii, Chem. Heterocycl.
Comp. 2001, 37, 1046-1047; b) I. V. Borovlev, O. P. Demidov, A. F.
Pozharskii, Russ. Chem. Bull. 2002, 51, 860.
[10] a) I. V. Borovlev, O. P. Demidov, A. F. Pozharskii, Chem. Heterocycl.
Comp. 2002, 38, 968-973; b) I. V. Borovlev, O. P. Demidov, A. F.
Pozharskii, Chem. Heterocycl. Comp. 2002, 38, 257-258.
[11] I. V. Borovlev, O. P. Demidov, A. V. Aksenov, A. F. Pozharskii, Russ. J.
Org. Chem. 2004, 40, 895.
Acknowledgements
This publication was supported by the Ministry of Education and
Science of the Russian Federation (the Agreement number
[12] a) A. V. Aksenov, I. V. Aksenova, A. S. Lyakhovnenko, D. A. Lobach,
Russ. Chem. Bull. 2009, 58, 859-861; b) A. V. Aksenov, M. H.
Magamadova, D. A. Lobach, I. V. Aksenova, I. V. Malikova, M. Rubin,
M. Chem. Heterocycl. Comp. 2014, 50, 1298-1304.
02.a03.21.0008).
Also, funds from the Russian Science
Foundation (grant #14-13-01108) to support synthetic studies
towards7H-Imidazo[4',5':4,5]benzo[1,2,3-gh]perimidine scaffolds
are gratefully acknowledged.
[13] See, for example: G. Ya. Reminnikov, L. K. Kurilenko, I. V. Boldyrev, V.
M. Cherkasov, Chem. Heterocycl. Comp. 1987, 23, 422-425; (Khim.
Geterocycl. Soedin. 1987, 508).
Keywords: pyrimidines•perimidines•1,3-diazapyrenes•peri-
[14] Other mineral (H2SO4, HCl, H3PO4) and strong organic (CF3COOH,
MeSO3H) acids were also tested. However, no formation of the target
material was observed in these cases. Reactions carried out in 86%
PPA carried out at temperatures lower than 250 oC were very sluggish
and did not proceed to completion. Reaction carried out in 80% PPA
(H4P2O7) proceeded very slowly even at 250 oC and accompanied by
formation of polymeric byproducts.
annulation•polyphosphoric acid
[1]
For reviews, see: a) C. Jia, B. Ma, N. Xin, X. Guo, Acc. Chem. Res.
2015, 48, 2565-2575; b) R. M. Metzger, Chem. Rev. 2015, 115, 5056-
5115; c) C. J. Lambert, Chem. Soc. Rev. 2015, 44, 875-888; d) C.
Wang, H. Dong, W. Hu, Y. Liu, D. Zhu, Chem. Rev. 2012, 112, 2208-
2267; e) J. E. Anthony, Angew. Chem., Int. Ed. 2008, 47, 452-483; f) B.
C. Thompson, J. M. J. Fréchet, Angew. Chem., Int. Ed. 2008, 47, 58-
77.
[15] A. F. Pozharskii, V. V. Kuz'menko, V. N. Koroleva, G. G. Yurchuk,
Chem. Heterocycl. Comp. 1980, 16, 541-546; (Khim. Geterotsikl.
Soedin. 1980, 691).
[16] Attempts to carry out this reaction at elevated temperature resulted in
partial decomposition of the product and lower yields of the product 20a.
Reactions performed at 60 oC and 80 oC afforded 73 and 64% yields,
respectively.
[2]
[3]
a) S. Geib, S. C. Martens, U. Zschieschang, F. Lombeck, H. Wadepohl,
H. Klauk, L. H. Gade, J. Org. Chem. 2012, 77, 6107-6116; b) S. C.
Martens, U. Zschieschang, H. Wadepohl, H. Klauk, L. H. Gade, Chem.-
Eur. J. 2012, 18, 3498-3509.
[17] A. Edel, P. A. Marnot, J. P. Sauvage, Tetrahedron Lett. 1985, 26, 727-
728.
I. Piantanida,V.Tomišić, M.Zinić, J. Chem. Soc., Perkin Trans. 2, 2000,
375-383.
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10.1002/ejoc.201601589
European Journal of Organic Chemistry
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
A highly efficient protocol for acid-
mediated peri-annulation of
Key Topic*
N
R1
N
N
N
R1
NH
R2
N
R3
R2
Alexander V. Aksenov,* Stanisvlav V.
Shcherbakov, Irina V. Lobach, Inna V.
Aksenova, and Michael Rubin*
86% PPA
perimidines with pyrimidines was
developed. Pyrimidines, used as
surrogates for 1,3-dicarbonyl
compounds allow for furnishing
benzo[gh]perimidines, including hardly
available analogs, non-substituted, or
mono-substituted at C-6, C-8.
R3
17 examples
N
R1
NH
Br
N
N
H
N
Page No. – Page No.
MeSO3H
Pyrimidines as surrogates for 1,3-
dicarbonyl compounds in peri-
annulation of perimidines en route to
1,3-diazapyrenes
8 examples
N
Br
R1
H2SO4
N
N
R1
N
N
+
HN
N
4 examples
*peri-annulation towards 1.3-diazapyrenes
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