New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation

Accepted Manuscript New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation Egor V. Verbitskiy, Oleg S. Eltsov, Ekaterina F. Zhilina, Ilya M. Pakhomov, Gennady L. Rusinov, Oleg N. Chupakhin, Valery N. Charushin PII:

S0040-4020(19)30346-1

DOI:

https://doi.org/10.1016/j.tet.2019.03.044

Reference:

TET 30230

To appear in:

Tetrahedron

Received Date: 29 January 2019 Revised Date:

21 March 2019

Accepted Date: 24 March 2019

Please cite this article as: Verbitskiy EV, Eltsov OS, Zhilina EF, Pakhomov IM, Rusinov GL, Chupakhin ON, Charushin VN, New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation, Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.03.044. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Graphical Abstract To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered.

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B(OH)2 Br

B(OH)2 Br Br

N Br

N

Suzuki cross-coupling

N

FeCl3

Oxidative Ar2 cyclodehydrogenation

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Suzuki cross-coupling

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Synthesis, Electrochemical and Optical properties

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N

Ar1

Ar1

N

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N

Ar1

Ar1

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New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation E.V. Verbitskiy, O.S. Eltsov, E.F. Zhilina, I.M. Pakhomov, G.L. Rusinov, O.N. Chupakhin, V.N. Charushin Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, 620990, Ekaterinburg, Russia Ar1 N N

Ar2

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New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation Egor V. Verbitskiya,b,*, Oleg S. Eltsovb, Ekaterina F. Zhilinaa, Ilya M. Pakhomov b, Gennady L. Rusinova,b, Oleg N. Chupakhina,b, and Valery N. Charushina,b Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str., 22, Ekaterinburg, 620990, Russia b Ural Federal University, Mira St. 19, Ekaterinburg, 620002, Russia E-mail: [email protected]

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Abstract An efficient synthetic route towards previously inaccessible dibenzo[f,h]quinazolines and [1]benzothieno[3,2-f]benzo[h]quinazolines through FeCl3-mediated intramolecular oxidative cyclodehydrogenation of readily available 5-([1,1'-biphenyl]-2-yl)pyrimidines and 5-(2phenylbenzo[b]thiophen-3-yl)pyrimidines is described. Molecular orbital calculations (DFT), as well as redox and photophysical measurements for all new compounds have been performed. The data show that the reported polycyclic systems have a potential to use in organic electronic applications.

Introduction

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Keywords: dibenzo[f,h]quinazoline, 1,3-diazatriphenylene, C-H functionalization

Fused π-conjugated heterocyclic systems are important core structural units of compounds that have found widespread applications in organic transistors, light emitting diodes and photovoltaics.1 1,3-Diazatriphenylene (I) and their thiophene analogues (II) have attracted much

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attention in supramolecular and materials chemistry, because of their rigid, planar, and conjugated structures, and also due to their self-assembling character (Figure 1).2,3 These

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compounds have found widespread applications in organic electronics as phosphorescent or electroluminescent host and/or hole transport materials.2 There are three main strategies for the synthesis of various dithienoquinazolines (Figure 2).4 Unfortunately, each of strategies has some limitations, such as: (a) a long reaction time for oxidative photocyclization (from 20 till 70 hours);4a (b) low yields (not exceeding 25%) for Pd-catalyzed intramolecular cyclization;4b (c) only those bi(hetero)aryl pyrimidines, that bear electron-donative substituents (for example, thienyl), can be used in intramolecular nucleophilic aromatic substitution reaction (SNH).4c,5 It is clear that these methods are of restricted use for the synthesis of dithienoquinazolines or

1

ACCEPTED MANUSCRIPT benzo[f]thieno[3,2-h]quinazolines.2 Therefore, new efficient synthetic strategies to achieve

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regioselective construction of unsymmetrical 1,3-triphenylenes remain to be challenging.

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Figure 1. Dibenzo[f,h]quinazoline (I), dithieno[3,2-f:2',3'-h]quinazoline (IIa) and dithieno[3,2-f:3',2'-h]quinazoline (IIb) derivatives.

Figure 2. State-of-the-art methods for preparation of dithienoquinazolines

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Result and Discussion Synthesis

The cross-dehydrogenative coupling (CDC) reactions6 can be regarded as a convenient synthetic methodology for the synthesis of numerous polycyclic aromatic hydrocarbons such as heterosuperbenzenes (HSB), as reported by Draper et al.7 The above-mentioned protocol, however, has only been used for the synthesis HSBs on the basis of substituted pyrimidines, bearing electron donating tert-butyl or methoxy groups. Taking into account the data previous studies and our research interests in elucidation of cross-coupling reactions, we wish herein to report

a

new

synthetic

protocol

for

preparation

of

unsymmetrically

substituted

2

ACCEPTED MANUSCRIPT dibenzo[f,h]quinazoline

and

[1]benzothieno[3,2-f]benzo[h]quinazoline

derivatives

via

intramolecular oxidative CDC. First of all, 5-(2-bromophenyl)pyrimidine (3) was obtained in 79% yield by using the Suzuki cross-coupling reaction of 5-bromopyrimidine (1) with 2-bromophenylboronic acid (2) (Scheme 1). The second starting material, 5-(2-Bromobenzo[b]thiophen-3-yl)pyrimidine (4), was

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obtained according to the earlier described4c procedure.

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Scheme 1. Synthesis of 5-(2-bromophenyl)pyrimidine (3).

As the next step, the series of 5-([1,1'-biphenyl]-2-yl)pyrimidines (6a-h) and 5-(2-

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phenylbenzo[b]thiophen-3-yl)pyrimidines (7a-h) have been synthesized in 60-90% yields

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(Scheme 2).

Scheme 2. Synthesis of 5-([1,1'-biphenyl]-2-yl)pyrimidines (6a-h) and 5-(2phenylbenzo[b]thiophen-3-yl)pyrimidines (7a-h).

We

have

started

our

studies

on

intramolecular

reactions

with

oxidative

cyclodehydrogenation of 5-(biphenyl-2-yl)pyrimidine (6a), varying oxidants and Lewis acids in order to find optimal reaction conditions (Table 1). It has been found that use of FeCl3 (4 equiv.) as oxidant and H2SO4 (1 equiv.) in anhydrous CHCl3 at room temperature for 24 h under argon atmosphere provides the best yield of the cyclization product 8a (Table 1, entry 2).

3

ACCEPTED MANUSCRIPT Table 1. Optimization of conditions for the synthesis of dibenzo[f,h]quinazoline (8a).

a

Isolated yield. bGC yield.

Yield (%)a 68 77 7b 2b 0 0 12 3b 44 18 65 39

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Lewis acid H2SO4 (1 equiv.) BF3·Et2O (2 equiv.) BF3·Et2O (2 equiv.) BF3·Et2O (2 equiv.) H2SO4 (1 equiv.) H2SO4 (1 equiv.) CF3SO3H (1 equiv.) CF3SO3H (1 equiv.) CF3SO3H (1 equiv.) CF3COOH (1 equiv.)

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Oхidant FeCl3 (4 equiv.) FeCl3 (4 equiv.) MoCl5 (2.5 equiv.) DDQ (2.5 equiv.) PIFA (2.5 equiv.) PhI(OAc)2 (2.5 equiv.) DDQ (2.5 equiv.) PIFA (2.5 equiv.) DDQ (2.5 equiv.) PIFA (2.5 equiv.) FeCl3 (4 equiv.) FeCl3 (4 equiv.)

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Entry 1 2 3 4 5 6 7 8 9 10 11 12

With the optimal reaction conditions found, we have elucidated the scope of intramolecular oxidative cyclodehydrogenation reaction to establish a diversity of substituents in arylpyrimidines which are admitted to convert these compounds into the corresponding 1,3-

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diazatriphenylenes 8 and 9 in 27-77 % yields (Scheme 3). The structure of 8c was established unequivocally by X-ray diffraction analysis (Figure 3). To our delight, both electron-donating (tBu and OMe) and electron-withdrawing inductively, but p-π donative (fluorine) groups in 5([1,1'-biphenyl]-2-yl)pyrimidines (6a-h) and 5-(2-phenylbenzo[b]thiophen-3-yl)pyrimidines (7a-

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h) are admitting conversion of the latter into the targeted products 8 and 9 in moderate-to-high yields. The exceptions are polycyclic compounds 8g, 9f and 9g, whose formation could not be detected even in the reaction mixtures by NMR. In two cases (compounds 8g and 9g) a low

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reactivity of arylpyrimidines 6g and 7g in intramolecular cyclizations can possibly be associated with inductive electron-withdrawing effects of two fluorine atoms in the benzene ring (both in the meta-positions relative to the reactive center, thus possessing a minimal p-π donative effect), while no conversion of 7f into 9f can hardly be explained in the frames of the suggested mechanism: the reaction was initiated by protonation of pyrimidine ring generate a pyrimidinium cation A, a subsequent intramolecular electrophilic aromatic substitution-type two-step process through the intermediates B and C to afford σH-adduct D, which is oxidized by FeCl3 and then is neutralized to produce the desired product 8 (or 9) (Scheme 4).

4

ACCEPTED MANUSCRIPT FeCl3 (4 equiv.), H2SO4 (1 equiv.), rt, 24 h.

Ar N

Ar N

CHCl3

N

N

R

6a-h 7a-h

R

8a-h, 9a-h

N N

MeO

8b, 61%

8d, 51%

N

N

N

8e'F

F

N

N

F

N

8g, 0%

8f, 59% F

N

9a, 67%

F

H3CO

N

N

N

9d, 28%

S

S

S

N

N N

F

N F

F

9g, 0% F

F

9h, 27%

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9f, 0% F

F

OCH3

9e'

40% (9e : 9e' = 7 : 1)

S

N

9c, 55% OCH3

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N

9e

9b, 72%

F

N

N

S

S N

S

N

N

N

F

8h, 32%

F

S

S N

N

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54% (8e : 8e' = 19 : 0.7)

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N

N

8e

OMe

8c, 69% OMe

N

F

N

N

N

8a, 77%

N

N

N

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6, 8 (Ar= Ph); 7, 9 (Ar= benzo[b]thiophen-3-yl)

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Scheme 3. Synthesis of dibenzo[f,h]quinazolines (8a-h) and [1]benzothieno[3,2-f]benzo[h]quinazolines (9a-h)

Figure 3. ORTEP of 8с with thermal ellipsoids are at 50% probability level.

5

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Scheme 4. A mechanism suggested for the intramolecular oxidative cyclodehydrogenation. It is worth noting that cyclizations of compounds 6e and 7e lead to the formation of

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mixtures of two regioisomeric products 8e/9e or 8e'/9e', which differ at which positions,

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C(10)/C(11) or C(12)/C(13), fluorine atoms are located, as shown in Scheme 5.

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Scheme 5. The structures of regioisomeric dibenzo[f,h]quinazolines (8e and 8e') and [1]benzothieno[3,2-f]benzo[h]quinazolines (9e and 9e')

In order to confirm unambiguously the structures and ratio of polycyclic compounds 8e/9e or 8e'/9e' two-dimensional HMBC 1H-13C and HSQC 1H–13C spectra were recorded for these compounds. The regioisomeric compounds 8e and 8e' were isolated in the ratio 19: 0.7. As for the major isomer 8e, all signals in the 1H and 13C NMR spectra of 8e have been assigned. In case of the minor isomer 8e', it could be possible to identify the signals of H(2), H(4) and H(8) protons (see Figure S1 in Supporting Information), the signals of other protons proved to be overlapping with signals of the major product. Unfortunately, the analysis of multiplicity and spin–spin coupling constants for proton resonance signals derived from the fluoroaromatic ring 6

ACCEPTED MANUSCRIPT did not allow us to differentiate between two isomeric structures 8e and 8e’. Therefore, the choice in favor of 8e was made on the basis of 2D NMR spectra, in which the characteristic signal of C(10) carbon resonance (doublet with J = 254 Hz) also exhibited 1H–13C couplings with three aromatic protons H(9), H(11) and H(12). In case of another structure (8e') the carbon, bearing a fluorine atom, would have interactions with only two aromatic protons. The most

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characteristic and informative features of the NMR data proved to be cross-peaks registered in two-dimensional HMBC spectra: C(10)/H(12), C(10)/H(11), C(10)/H(9); C(12b)/H(12), H(4), H(2); C(8b)/H(12), H(8), H(5); C(11)/H(12), H(9); C(12a)/H(11), H(9); C(8)/H(6), H(7) (Figure

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4).

Figure 4. 2D NMR gHMBC (600 MHz, CDCl3) spectrum of 8e at 298 K.

In a similar way the 2D NMR gHMBC and gHSQC spectral data enabled us to assign all protons and carbon resonance signals for the major product 9e (see Figures S2 and S3 in Supporting Information). The most characteristic and informative features of NMR data for compound 9e are cross-peaks in two-dimensional HMBC: С(13b)/H(2), H(4), H(13); C(4b)/H(4), H(5); C(9b) / H(13); C(11) / H(10), H(12), H(13); C(4c) / H(6), H(8); C(13a) / H(12); C(8a) / H(5), H(7) (see Figures S2 in Supporting Information). 7

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Photophysical and Electrochemical Properties The

optical

properties

of

dibenzo[f,h]quinazolines

(8a-c),

[1]benzothieno[3,2-

f]benzo[h]quinazolines (9a-c) and unsubstituted triphenylene as a standard were investigated

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with UV/Vis and photoluminescence spectroscopy in CH2Cl2 solutions at room temperature. The data obtained are summarized in Table 2 and are given in Figures 5 and S4-S11 in Supporting Information.

The positions of the observed maxima in the series 8a-c and 9a-c have one tendency and

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depend on the substituent in the phenyl moiety. Incorporation of an electron-donating group (H→t-Bu→OMe) results in a bathochromic shift of the absorption maxima. It should be noted that the presence of nitrogen atoms leads to a hypsochromic shift of the absorption maximum in

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the spectrum of 8a in comparison with the spectrum of triphenylene due to the existing inductive effect.

In contrast to the triphenylene, the dibenzo[f,h]quinazolines (8a-c) and [1]benzothieno[3,2f]benzo[h]quinazolines (9a-c) show one emission maximum in fluorescence spectra in dichloromethane solution at room temperature. In addition, the introduction of methoxy groups leads to a more significant bathochromic shift of the fluorescence maximum in comparison with

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the t-Bu group: 58 nm vs 8 nm for 8a-c and 14 nm vs 2 nm for 9a-c, respectively. The fluorescence efficiency of 9a-c (ΦF = 0.08-0.10) is approximately three times higher than that for the 8a-c (ΦF = 0.01-0.04) (Table 2). The increase of the fluorescence quantum yields can be explained by the presence of a benzothienyl group, which enhance the π-

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conjugation in compounds 9a-c.

Table 2. UV/Vis and photoluminescence data for 8a-c, 9a-c and triphenylene. Absorption λmax, nm (ε, 103 L mol-1cm-1)

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Compound

8a

8b

8c 9a

346 (1.5), 329 (1.9), 256 (54.8) 348 (3.2), 332 (3.9), 280 (23.6) 353 (2.9), 270 (80.2) 375 (5.9), 357 (5.4), 326 (18.4),

Photoluminescence Excitation Emission λmax, nm λmax, nm 346, 368 329, 256 348, 376 332, 280

375, 357, 326,

412

ΦF[a] < 0.01

0.03

0.08

8

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314 (17.5), 314, 271 (54.1), 271, 262 (50.4), 262, 241 (35.8) 271 377 (6.0), 377, 414 0.10 9b 360 (5.3), 360, 326 (16.6), 326, 315 (17.0), 315, 272 (54.7), 277, 242 (32.7) 242 376 (6.8), 376, 426 0.09 9c 357 (6.0), 357, 322 (15.6), 322, 277 (63.3), 277, 246 (24.3) 246 Triphenylene 286 (13.4), 286, 355, 364, 371 0.02 260 (102.7), 260, 251 (60.5) 251 [a] Fluorescence quantum yield (± 10 %) determined relative to 2-aminopyridine in 0.05 M H2SO4 as standard (ΦF = 0.60).8 Excitation at 260 nm.

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Figure 5. UV/Vis spectra of compounds 8a-c and triphenylene in dichloromethane at room temperature The cyclic voltammetry (CV) was performed on the six basic dibenzo[f,h]quinazolines (8ac) and [1]benzothieno[3,2-f]benzo[h]quinazolines (9a-c) to determine their redox potentials (see Table

3).

Unfortunately,

in

the

accessible

range

of

potentials

[analogously

to

4a

dithienoquinazolines ], no distinct oxidation or reduction maxima were observed for the compounds 8a and 8b. The cyclic voltammograms shown in Figures S12–S15 demonstrate the irreversible character of oxidation of 1,3-diazatriphenylene derivatives 8c and 9a–c. Given that no cathodic behavior of compounds 8c and 9a–c could be recorded by CV, their excited state reduction potentials (corresponding to the LUMO energy levels) were calculated by adding the 9

ACCEPTED MANUSCRIPT energy gap Egopt (estimated from the long-wavelength absorption edge of the absorption spectra recorded in CH2Cl2 solution) to the HOMO energy values (Table 3). Table 3. Electrochemical properties of the dibenzo[f,h]quinazolines (8a-c) and [1]benzothieno[3,2-f]benzo[h]quinazolines (9a-c). Eoxonset[a]

EHOMO, ELUMO*, eV eV[b]

Egopt , eV[c]

EHOMOcalc [d] , eV

ELUMOcalc , eV[d]

Egcalc , eV[d]

-6.38

-1.76

4.62

-6.01

-1.75

4.26

-5.91

-1.52

4.39

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En Polycycle try 8a

-

-

-

3.51

2

8b

-

-

-

3.45

3

8c

0.89

-5.99

-2.61

3.38

4

9a

1.04

-6.14

-2.97

3.17

-6.03

-1.96

4.07

5

9b

1.02

-6.12

-2.99

3.13

-5.92

-1.88

4.04

6

9c

0.86

-5.96

-2.80

3.16

-5.84

-1.82

4.02

7

Triphenylene

-

-6.05[e]

-1.90[e]

4.15[e]/4.13

-5.30[f]

-1.81[f]

3.49[f]

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Eoxonset – Onset oxidation potential (vs Ag/AgNO3 reference electrode); ELUMO* = EHOMO + Eg; [c] Energy gap estimated from the onset of the absorption spectra recorded in CH2Cl2 solution (Egopt=1240/λonset); [d] Calculations for compounds 8a-c and 9a-c were performed by using density-functional theory at the B3LYP/631G* level; [e] Electrochemically measured (solution in CH2Cl2) frontier orbital energies and energy band gap for triphenylene (see Ref. 9); [f] Calculations for triphenylene were performed by using density-functional theory at the B88LYP-DZVP level (see Ref. 9). [a]

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[b]

As expected, theoretically predicted energies of the HOMO, the LUMO, and the energy

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gap (Table 3) differ from those that were obtained experimentally, due to approximate character of the exchange-correlation functional employed. Nevertheless, the trends in the series of 8a-c and 9a-c, calculated theoretically and determined experimentally, appear to be the same from a

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qualitative point of view.

The unsubstituted triphenylene will function as reference in the following discussion on relative changes in frontier orbital energies (Table 3, entry 7). All selected compounds (8a-c and 9a-c) are wide band gap semiconductors of 3.39-3.94 eV for 8a-c and 3.13-4.317 eV for 9a-c. The measured optical band gap values for 8a-c and 9a-c appear to be typical for semiconducting thienoacenes4 (~3.0-3.5 eV) and much less than for the triphenylene (4.13 eV). Thus, pyrimidine ring in polycycles 8 and 9 leads to a relatively large reduction of the band gap due to the donor– acceptor-like structure. Moreover, incorporation of the nitrogen-rich ring leads to a much larger reduction in LUMO (∆E= 0.70–1.09) than HOMO (∆E= 0.07-0.09). This finding suggests that 10

ACCEPTED MANUSCRIPT increasing the nitrogen content in structurally similar compounds could lead to very low LUMO levels and may be a useful strategy for the design of n-type semiconductors. Note that, in general, air-stable p-channel FET operation is known to be implemented with the organic semiconductors with HOMO energy levels lower than 5.0 eV.10 Along with these criteria, the present thienoacenes seem to be promising options for potential development of airstable organic

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field-effect transistors (OFETs).

Conclusions

In summary, we have developed a new approach for the synthesis of unsymmetrical 1,3-

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diazatriphenylenes via intramolecular oxidative cyclodehydrogenation of the corresponding 5phenylaryl(hetaryl) substituted pyrimidines. The present synthetic procedure provides a facile

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way to the family of nitrogen-containing polycyclic heteroaromatic compounds that can potentially be used in organic electronics and luminescent materials.

Experimental Section

General Information. All reagents and solvents were obtained from commercial sources and dried by using standard procedures before use. The 1H, 19F, and 13C NMR spectra were recorded

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on a Bruker DRX-400, AVANCE-500 and AVANCE-600 instruments using Me4Si and C6F6 as an internal standards. All signals in the 1H and 13C NMR spectra were assigned on the basis of 2D 1H–13C gHSQC and gHMBC experiments. Elemental analysis was carried on a Eurovector EA 3000 automated analyzer. Melting points were determined on Boetius combined heating

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stages and were not corrected.

Flash-column chromatography was carried out using Alfa Aesar silica gel 0.040-0.063 mm

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(230–400 mesh), eluting with ethyl acetate-hexane. The progress of reactions and the purity of compounds were checked by TLC on Sorbfil plates (Russia), in which the spots were visualized with UV light (λ 254 or 365 nm). Cyclic voltammetry was carried out on a Metrohm Autolab PGSTAT128N potentiostat

with a standard three-electrode configuration. Typically, a three electrodes cell equipped with a platinum working electrode, a Ag/AgNO3 (0.01M) reference electrode, and a glass carbon rod counter electrode was employed. The

measurements were done in CH2Cl2 with

tetrabutylammonium perchlorate (0.1 M) as the supporting electrolyte under an argon atmosphere at a scan rate of 100 mV/s. The potential of reference electrode was calibrated by using the ferrocene/ferrocenium redox couple (Fc/Fc+), which has a known oxidation potential of 11

ACCEPTED MANUSCRIPT +5.1 eV vs. vacuum for ferrocene.11 The HOMO energy values were estimated from the onset potentials (Eoxonset) of the first oxidation event according to the following equations: EHOMO (eV) = – [Eoxonset – E1/2(Fc/Fc+) + 5.1] where E1/2(Fc/Fc+) is the half-wave potential of the Fc/Fc+ couple against the Ag/AgNO3 electrode.

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Geometry optimization and energy calculation for polycycles 8a-c and 9a-c were performed by using density-functional theory at the B3LYP/6-31G* level with the ORCA 4.0.3 program12 (Figures S16 and S17 in Supporting Information).

The XRD experiment was performed on a Xcalibur 3 diffractometer on standard procedure

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(MoK-irradiation, graphite monochromator, ψ- and ω-scans with 1o step at T= 295(2) K). Empirical absorption correction was applied. The structure was solved and refined using the Olex2 software package.13 The structure was solved by the direct method using ShelXS

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program14 and refined by full-matrix least squares method against F2 using ShelXL program in anisotropic approximation for non-hydrogen atoms; H-atoms were refined isotropically in the «rider» model. The X-ray crystallography data for structure reported in this paper have been deposited with Cambridge Crystallography Data Centre as supplementary publications CCDC 1885101 for 8c. These data can be obtained free of charge from the Cambridge Crystallographic

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Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

5-(2-Bromophenyl)pyrimidine (3). A mixture of 5-bromopyrimidine (1) (3.82 g, 24.0 mmol), 2-bromophenylboronic acid 2 (4.02 g, 20.0 mmol), Pd(PPh3)4 (1.16 g, 5 mol %) and K3PO4(530 mg, 2.5 mmol) was dissolved in 1,4-dioxane 80 mL. The reaction mixture was degassed and

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refluxed for 20 h under an argon atmosphere. After completion of the reaction (monitored by TLC), 100 mL water was added and extracted with ethyl acetate. The combined organic layer was washed with water, brine, and dried over anhydrous Na2SO4 and concentrated in vacuo. The

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crude product was purified by column chromatography on silica gel with EtOAc/hexane (1:2, v/v) as an eluent to give 3 (3.71 g, 79 %) as a pale yellow solid, mp 56-58 °С. 1H NMR (500 MHz, DMSO) δ 9.26 (s, 1H), 8.92 (s, 2H), 7.83 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 4.2 Hz, 2H), 7.47–7.42 (m, 1H).

13

C NMR (126 MHz, DMSO) δ 157.5, 156.7, 135.2, 134.1, 133.1, 131.7,

130.8, 128.4, 122.0. Calcd. for C10H7BrN2 (235.08): C, 51.09; H, 3.00; N, 11.92. Found: C, 51.02; H, 3.11; N, 11.96. General procedure for the synthesis of 5-(biphenyl-2-yl)pyrimidine (6a-h) and 5-(2phenylbenzo[b]thiophen-3-yl)pyrimidine (7a-h) derivatives.

12

ACCEPTED MANUSCRIPT A mixture of 5-(2-bromophenyl)pyrimidine (3) [or 5-(2-bromobenzo[b]thiophen-3-yl)pyrimidine (4)] (1.0 mmol), corresponding arylboronic acid 5a-h (1.2 mmol), Pd(PPh3)4 (58 mg, 5 ol %) and K3PO4 (530 mg, 2.5 mmol) was dissolved in 1,4-dioxane 15 mL. The reaction mixture was degassed and refluxed for an appropriate time under an argon atmosphere. After completion of the reaction (monitored by TLC), 10 mL water was added and extracted with ethyl acetate. The

RI PT

combined organic layer was washed with water, brine, and dried over anhydrous Na2SO4 and concentrated in vacuo. Purification by silica gel column chromatography with EtOAc/hexane (1:2, v/v) as an eluent to afford the title compounds (6a-h or 7a-h).

5-(Biphenyl-2-yl)pyrimidine (6a). The reaction time is 15 hours. Yield 184 mg, 79%, white

SC

crystals, mp 104-106 °С. 1H NMR (500 MHz, DMSO) δ 9.03 (s, 1H), 8.52 (s, 2H), 7.60–7.55 (m, 3H), 7.49 (dt, J = 6.5, 1.6 Hz, 1H), 7.33–7.27 (m, 3H), 7.15–7.13 (m, 2H).

13

C NMR (126

M AN U

MHz, DMSO) δ 156.7, 156.4, 140.6, 139.9, 134.4, 132.9, 130.6, 130.5, 129.8, 129.1, 128.3, 128.1, 127.1. Calcd. for C16H12N2 (232.28): C, 82.73; H, 5.21; N, 12.06. Found: C, 82.64; H, 5.13; N, 11.92.

5-(4'-Tert-butylbiphenyl-2-yl)pyrimidine (6b). The reaction time is 15 hours. Yield 173 mg, 60%, white powder, mp 90-91 °С. 1H NMR (500 MHz, CDCl3) δ 9.06 (s, 1H), 8.52 (s, 2H), 7.52–7.45 (m, 3H), 7.40 (d, J = 6.9 Hz, 1H), 7.30–7.27 (m, 2H), 7.05–7.02 (m, 2H), 1.30 (s, 9H). 13

TE D

C NMR (126 MHz, CDCl3) δ 156.9, 156.1, 150.4, 141.1, 136.8, 135.4, 132.8, 131.1, 130.2,

129.6, 129.2, 127.9, 125.4, 34.5, 31.36. Calcd. for C20H20N2 (288.39): C, 83.30; H, 6.99; N, 9.71. Found: C, 83.27; H, 7.08; N, 9.63.

5-(3',4',5'-Trimethoxybiphenyl-2-yl)pyrimidine (6c). The reaction time is 20 hours. Yield 284

EP

mg, 88%, beige powder, mp 110-111 °С. 1H NMR (500 MHz, CDCl3) δ 9.08 (s, 1H), 8.57 (s, 2H), 7.53–7.49 (m, 3H), 7.43 (d, J = 6.8 Hz, 1H), 6.30 (s, 2H), 3.84 (s, 3H), 3.67 (s, 6H).

13

C

NMR (126 MHz, CDCl3) δ 156.6, 156.2, 153.1, 141.1, 137.5, 135.3, 135.2, 132.7, 130.7, 130.2,

AC C

129.3, 128.2, 107.4, 60.9, 56.0. Calcd. for C19H18N2O3 (322.36): C, 70.79; H, 5.63; N, 8.69. Found: C, 70.71; H, 5.47; N, 8.54. 5-(2'-Fluorobiphenyl-2-yl)pyrimidine (6d). The reaction time is 20 hours. Yield 197 mg, 79%, white powder, mp 73-74 °С. 1H NMR (500 MHz, CDCl3) δ 9.06 (s, 1H), 8.53 (s, 2H), 7.56–7.52 (m, 2H), 7.50–7.45 (m, 1H), 7.45–7.41 (m, 1H), 7.28 (ddd, J = 13.4, 6.2, 1.7 Hz, 1H), 7.23 (td, J = 7.5, 1.6 Hz, 1H), 7.13 (td, J = 7.5, 0.8 Hz, 1H), 6.93 (t, J = 9.1 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 158.8 (d, 1J = 247.0 Hz), 156.5 (m), 156.3, 134.2 (dd, 4J = 3.3, 4J = 1.7 Hz), 131.8 (d, 4

J = 3.2 Hz), 131.3, 130.0 (d, 3J = 8.3 Hz), 129.7, 129.1, 128.8, 127.64, 127.63, 127.5, 124.4 (d,

4

J = 3.6 Hz), 115.9 (d, 2J = 22.2 Hz). 19F NMR (471 MHz, CDCl3) δ 46.97 (ddd, J = 9.9, 7.4, 5.2 13

ACCEPTED MANUSCRIPT Hz). Calcd. for C16H11FN2 (250.27): C, 76.79; H, 4.43; N, 11.19. Found: C, 76.69; H, 4.42; N, 11.08. 5-(3'-Fluorobiphenyl-2-yl)pyrimidine (6e). The reaction time is 16 hours. Yield 233 mg, 93%, white powder, mp 112-113 °С. 1H NMR (500 MHz, CDCl3) δ 9.07 (s, 1H), 8.52 (s, 2H), 7.56– 7.50 (m, 2H), 7.50–7.46 (m, 1H), 7.46–7.41 (m, 1H), 7.23 (td, J = 8.0, 6.0 Hz, 1H), 6.96 (td, J =

RI PT

8.3, 2.2 Hz, 1H), 6.88–6.84 (m, 2H). 3C NMR (126 MHz, CDCl3) δ 162.6 (d, 1J = 247.2 Hz), 156.8, 156.6, 142.2 (d, 3J = 7.6 Hz), 139.9, 134.7, 132.9, 130.9, 130.3, 130.0 (d, 3J = 8.5 Hz), 129.3, 128.6, 125.7 (d, 4J = 2.8 Hz), 116.8 (d, 2J = 21.8 Hz), 114.4 (d, 2J = 21.0 Hz). 19F NMR (471 MHz, CDCl3) δ 49.32 (td, J = 8.9, 6.0 Hz). Anal. Calcd for C16H11FN2 (250.27): C, 76.79;

SC

H, 4.43; N, 11.19. Found: C, 76.70; H, 4.24; N, 11.31.

5-(4'-Fluorobiphenyl-2-yl)pyrimidine (6f). The reaction time is 15 hours. Yield 210 mg, 84%,

M AN U

white powder, mp 83-84 °С. 1H NMR (500 MHz, CDCl3) δ 9.07 (s, 1H), 8.50 (s, 2H), 7.53–7.50 (m, 2H), 7.47–7.45 (m, 1H), 7.43–7.41 (m, 1H), 7.11–7.05 (m, 2H), 7.00–6.94 (m, 2H). 1

13

C

4

NMR (126 MHz, CDCl3) δ 162.1 (d, J = 247.6 Hz), 156.9, 156.5, 140.1, 135.9 (d, J = 3.5 Hz), 135.0, 132.9, 131.5 (d, 3J = 8.2 Hz), 131.0, 130.3, 129.3, 128.3, 115.6 (d, 2J = 21.5 Hz).

19

F

NMR (471 MHz, CDCl3) δ 47.11 (tt, J = 8.6, 5.3 Hz). Calcd. for C16H11FN2 (250.27): C, 76.79; H, 4.43; N, 11.19. Found: C, 76.59; H, 4.32; N, 11.08.

TE D

5-(2',4'-Difluorobiphenyl-2-yl)pyrimidine (6g). The reaction time is 20 hours. Yield 172 mg, 64%, white powder, mp 120-122 °С. 1H NMR (500 MHz, CDCl3) δ 9.08 (s, 1H), 8.53 (s, 2H), 7.58–7.53 (m, 2H), 7.46–7.41 (m, 2H), 7.20 (td, J = 8.5, 6.4 Hz, 1H), 6.91–6.86 (m, 1H), 6.70 (ddd, J = 9.8, 8.9, 2.5 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 162.8 (dd, 1J = 250.2, 3J = 11.5

EP

Hz), 159.0 (dd, 1J = 249.5, 3J = 11.9 Hz), 156.6, 156.3, 134.9, 134.3, 134.1, 132.5 (dd, 3J = 9.5, 4

J = 4.7 Hz), 131.4, 129.9, 129.2, 129.0, 123.8 (dd, 2J = 15.3, 4J = 3.6 Hz), 111.9 (dd, 2J = 21.2,

4

J = 3.6 Hz), 104.4 (t, 2J = 25.8 Hz). 19F NMR (376 MHz, CDCl3) δ 52.29 – 52.17 (m, 1F), 51.61

AC C

(dd, J = 17.7, 8.8 Hz, 1F). Calcd. for C16H10F2N2 (268.26): C, 71.64; H, 3.76; N, 10.44. Found: C, 71.51; H, 3.62; N, 10.42.

5-(3',5'-Difluorobiphenyl-2-yl)pyrimidine (6h). The reaction time is 20 hours. Yield 241 mg, 90%, white powder, mp 112-113 °С. 1H NMR (500 MHz, CDCl3) δ 9.11 (s, 1H), 8.53 (s, 2H), 7.58–7.52 (m, 2H), 7.45 (qd, J = 5.1, 2.9 Hz, 2H), 6.72 (tt, J = 8.9, 2.2 Hz, 1H), 6.68–6.62 (m, 2H).

13

C NMR (126 MHz, CDCl3) δ 162.8 (d, 1J = 249.8 Hz), 162.7 (d, 1J = 249.9 Hz), 157.0,

156.7, 143.3 (t, 3J = 9.5 Hz), 138.8, 134.3, 132.9, 130.6 (d, J = 24.9 Hz), 129.3, 129.0, 112.9 (dd, 2

J = 19.4, 3J = 6.2 Hz), 103.0 (t, 2J = 25.2 Hz). 19F NMR (471 MHz, CDCl3) δ 53.28–52.50 (m,

14

ACCEPTED MANUSCRIPT 2F). Calcd. for C16H10F2N2 (268.26): C, 71.64; H, 3.76; N, 10.44. Found: C, 71.72; H, 3.70; N, 10.36. 5-(2-Phenylbenzo[b]thiophen-3-yl)pyrimidine (7a). The reaction time is 17 hours. Yield 179 mg, 69%, beige crystals, mp 138-140 °С. 1H NMR (400 MHz, DMSO) δ 9.23 (s, 1H), 8.79 (s, 1H), 8.12 (dd, J = 6.7, 1.8 Hz, 1H), 7.60–7.56 (m, 1H), 7.52–7.43 (m, 2H), 7.43–7.32 (m, 5H). 13

RI PT

C NMR (101 MHz, DMSO) δ 157.7, 157.3, 141.8, 139.4, 138.2, 132.6, 129.6, 129.1, 128.9,

128.6, 126.1, 125.4, 125.3, 122.6, 122.4. Calcd. for C18H12N2S (288.37): C, 74.97; H, 4.19; N, 9.71. Found: C, 74.98; H, 4.06; N, 9.74.

5-(2-(4-Tert-butylphenyl)benzo[b]thiophen-3-yl)pyrimidine (7b). The reaction time is 20

SC

hours. Yield 289 mg, 84%, white powder, mp 126-127 °С. 1H NMR (500 MHz, CDCl3) δ 9.23 (s, 1H), 8.76 (s, 2H), 7.95–7.88 (m, 1H), 7.58–7.53 (m, 1H), 7.43–7.38 (m, 2H), 7.33 (d, J = 8.4 13

C NMR (126 MHz, CDCl3) δ 157.9, 156.7,

M AN U

Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 1.31 (s, 9H).

151.9, 143.3, 139.6, 139.1, 130.2, 129.7, 129.4, 125.9, 125.2, 125.1, 124.7, 122.4, 121.9, 34.7, 31.2. Calcd. for C22H20N2S (344.47): C, 76.71; H, 5.85; N, 8.13. Found: C, 76.78; H, 5.96; N, 7.98.

5-(2-(3,4,5-Trimethoxyphenyl)benzo[b]thiophen-3-yl)pyrimidine (7c). The reaction time is 15 hours. Yield 280 mg, 74%, white powder, mp 138-140 °С. 1H NMR (500 MHz, CDCl3) δ 9.24 3.86 (s, 3H), 3.69 (s, 6H).

TE D

(s, 1H), 8.79 (s, 2H), 7.94–7.90 (m, 1H), 7.59–7.55 (m, 1H), 7.46–7.40 (m, 2H), 6.47 (s, 2H), 13

C NMR (126 MHz, CDCl3) δ 157.9, 156.82, 156.80, 153.4, 143.0,

139.4, 138.9, 138.5, 130.2, 128.0, 125.3, 125.1, 122.4, 122.0, 107.1, 60.9, 56.0. Calcd. for C21H18N2O3S (378.44): C, 66.65; H, 4.79; N, 7.40. Found: C, 66.59; H, 4.63; N, 7.35

EP

5-[2-(2-Fluorophenyl)benzo[b]thiophen-3-yl]pyrimidine (7d). The reaction time is 20 hours. Yield 251 mg, 82%, white powder, mp 36-38 °С. 1H NMR (500 MHz, CDCl3) δ 9.18 (s, 1H), 8.71 (s, 2H), 7.96–7.91 (m, 1H), 7.66–7.58 (m, 1H), 7.48–7.42 (m, 2H), 7.41–7.31 (m, 2H), 7.17

AC C

(td, J = 7.5, 0.8 Hz, 1H), 7.03 (t, J = 8.9 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 159.2 (d, 1J = 250.3 Hz), 157.2, 156.1, 139.9, 138.7, 135.7, 132.5 (d, 4J = 2.1 Hz), 131.1 (d, 3J = 8.2 Hz), 129.8, 128.3, 125.3 (d, 2J = 18.9 Hz), 124.5 (d, 4J = 3.7 Hz), 122.5, 122.2, 120.7, 120.6, 116.4 (d, 2

J = 21.9 Hz). 19F NMR (471 MHz, CDCl3) δ 49.71 (ddd, J = 10.0, 7.3, 5.2 Hz, 1F). Calcd. for

C18H11FN2S (306.36): C, 70.57; H, 3.62; N, 9.14. Found: C, 70.52; H, 3.46; N, 8.98. 5-[2-(3-Fluorophenyl)benzo[b]thiophen-3-yl]pyrimidine (7e). The reaction time is 20 hours. Yield 270 mg, 88%, white powder, mp 124-126 °С. 1H NMR (500 MHz, DMSO) δ 9.25 (s, 1H), 8.81 (s, 2H), 8.15–8.13 (m, 1H), 7.60–7.58 (m, 1H), 7.53–7.48 (m, 2H), 7.47–7.42 (m, 1H), 7.27–7.20 (m, 1H), 7.17 (dd, J = 9.2, 1.9 Hz, 2H). 13C NMR (126 MHz, DMSO) δ 161.91 (d, 1J 15

ACCEPTED MANUSCRIPT = 245.2 Hz), 157.8, 157.5, 140.0 (d, 4J = 2.2 Hz), 139.2, 138.2, 134.9 (d, 3J = 8.4 Hz), 131.0 (d, 3

J = 8.6 Hz), 128.7, 126.9, 125.9 (d, 4J = 2.8 Hz), 125.63, 125.55, 122.7, 122.6, 116.4 (d, 2J =

22.6 Hz), 115.6 (d, 2J = 20.9 Hz).

19

F NMR (471 MHz, DMSO) δ 50.50–50.45 (m, 1F). Calcd.

for C18H11FN2S (306.36): C, 70.57; H, 3.62; N, 9.14. Found: C, 70.56; H, 3.71; N, 9.13. 5-[2-(4-Fluorophenyl)benzo[b]thiophen-3-yl]pyrimidine (7f). The reaction time is 10 hours.

RI PT

Yield 248 mg, 81%, white powder, mp 132-134 °С. 1H NMR (500 MHz, DMSO) δ 9.23 (s, 1H), 8.80 (s, 2H), 8.12 (d, J = 7.4 Hz, 1H), 7.58–7.56 (m, 1H), 7.48 (dq, J = 7.1, 6.0 Hz, 2H), 7.41– 7.37 (m, 2H), 7.27–7.22 (m, 2H). 13C NMR (126 MHz, DMSO) δ 162.05 (d, 1J = 247.1 Hz), 157.7, 157.3, 140.5, 139.2, 138.1, 131.8 (d, 3J = 8.5 Hz), 128.9 (d, 4J = 3.3 Hz), 128.8, 126.3,

SC

125.41, 125.35, 122.6, 122.4, 115.9 (d, 2J = 21.9 Hz). 19F NMR (471 MHz, DMSO) δ 50.03 (tt, J = 8.9, 5.4 Hz, 1F). Calcd. for C18H11FN2S (306.36): C, 70.57; H, 3.62; N, 9.14. Found: C, 70.38;

M AN U

H, 3.51; N, 9.24.

5-[2-(2,4-Difluorophenyl)benzo[b]thiophen-3-yl]pyrimidine (7g). The reaction time is 15 hours. Yield 220 mg, 68%, pale yellow powder, mp 42-43 °С. 1H NMR (500 MHz, CDCl3) δ 9.20 (s, 1H), 8.70 (s, 2H), 7.96–7.92 (m, 1H), 7.62 (dd, J = 6.5, 2.4 Hz, 1H), 7.48–7.42 (m, 2H), 7.37 (td, J = 8.4, 6.4 Hz, 1H), 6.92 (td, J = 8.1, 2.2 Hz, 1H), 6.80 (td, J = 9.7, 2.5 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 163.4 (dd, 1J = 253.0, 3J = 12.1 Hz), 159.5 (dd, 1J = 253.4, 3J = 12.8

TE D

Hz), 157.4, 157.2, 139.8, 138.7, 134.5, 133.4 (d, 4J = 3.7 Hz), 133.3 (d, 4J = 3.8 Hz), 129.6, 128.7, 125.4 (d, 2J = 24.8 Hz), 122.4 (d, 2J = 21.9 Hz), 116.9 (d, 4J = 4.2 Hz), 116.8 (d, 4J = 3.9 Hz), 112.1 (dd, 2J = 21.4, 4J = 3.9 Hz), 104.9 (t, 2J = 25.7 Hz).

19

F NMR (471 MHz, CDCl3) δ

54.49–54.42 (m, 1F), 54.34 (dd, J = 18.0, 9.0 Hz, 1F). Calcd. for C18H10F2N2S (324.35): C,

EP

66.65; H, 3.11; N, 8.64. Found: C, 66.71; H, 3.15; N, 8.56. 5-[2-(3,5-Difluorophenyl)benzo[b]thiophen-3-yl]pyrimidine (7h). The reaction time is 16 hours. Yield 247 mg, 76%, white powder, mp 121-123 °С.1H NMR (500 MHz, CDCl3) δ 9.26 (s,

AC C

1H), 8.73 (s, 2H), 7.96–7.90 (m, 1H), 7.60–7.57 (m, 1H), 7.45 (pd, J = 7.1, 1.2 Hz, 2H), 6.82– 6.76 (m, 3H).

13

C NMR (126 MHz, CDCl3) δ 163.0 (dd, 1J = 250.5, 3J = 13.1 Hz), 157.80,

157.75, 139.7 (t, 4J = 2.6 Hz), 139.2 (d, 2J = 20.3 Hz), 136.07, 136.06 (d, 2J = 20.1 Hz), 129.1, 127.0, 125.8, 125.5, 122.5 112.9 (d, 3J = 6.6 Hz), 112.8 (d, 3J = 6.7 Hz), 104.2 (t, 2J = 25.2 Hz). 19

F NMR (471 MHz, CDCl3) δ 53.85–53.78 (m, 2F). Calcd. for C18H10F2N2S (324.35): C, 66.65;

H, 3.11; N, 8.64. Found: C, 66.53; H, 3.06; N, 8.58. General

procedure

for

the

synthesis

of

dibenzo[f,h]quinazoline

(8a-h)

and

[1]benzothieno[3,2-f]benzo[h]quinazoline (9a-h) derivatives. Corresponding 5-(biphenyl-2yl)pyrimidine (6a-h) and 5-(2-phenylbenzo[b]thiophen-3-yl)pyrimidine (7a-h) derivatives (1.0 16

ACCEPTED MANUSCRIPT mmol) were dissolved in dehydrated CHCl3 (10 mL). The air in the flask was replaced with argon. Then, concentrated sulfuric acid (53 µL, 1.0 mmol) and iron(III) chloride (649 mg, 4.0 mmol) were added to this solution. The resulting mixture was stirred for 24 h at room temperature, diluted with aqueous ammonia (15 mL), a precipitate formed and was filtered off, washed with water and air-dried. The residue was purified by flash column chromatography

RI PT

(eluent EtOAc–hexane, gradient from 1:2 to 100% EtOAc) to afford the desired dibenzo[f,h]quinazoline (8a-h) and [1]benzothieno[3,2-f]benzo[h]quinazoline (9a-h) derivatives. Dibenzo[f,h]quinazoline (8a). Yield 177 mg, 77%, white powder, mp 176-178 °С. 1H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 9.45 (s, 1H), 9.28 (d, J = 8.1 Hz, 1H), 8.63 (dd, J = 14.1, 7.6

SC

Hz, 3H), 7.86 (t, J = 7.5 Hz, 1H), 7.75 (dt, J = 14.6, 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 156.1, 153.4, 151.1, 133.0, 130.9, 129.7, 128.8, 128.7, 127.9, 127.8, 126.7, 125.6, 123.5, 122.7,

M AN U

122.4, 121.2. Calcd. for C16H10N2 (230.26): C, 83.46; H, 4.38; N, 12.17. Found: C, 83.38; H, 4.39; N, 12.23.

11-Tert-butyldibenzo[f,h]quinazoline (8b). Yield 175 mg, 61%, off-white powder, mp 159-160 °С. 1H NMR (500 MHz, CDCl3) δ 10.01 (s, 1H), 9.49 (s, 1H), 9.34 (d, J = 2.1 Hz, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.62 (d, J = 8.2 Hz, 1H), 8.60 (d, J = 8.7 Hz, 1H), 8.01 (dd, J = 8.6, 2.2 Hz, 1H), 7.84 – 7.79 (m, 1H), 7.79–7.74 (m, 1H), 1.53 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 13C NMR

TE D

(101 MHz, CDCl3) δ 156.1, 153.5, 151.5, 151.1, 130.8, 129.9, 129.0, 128.7, 128.6, 127.6, 126.7, 123.4, 122.7, 122.4, 121.6, 121.4, 35.2, 31.4. Calcd. for C20H18N2 (286.37): C, 83.88; H, 6.34; N, 9.78. Found: C, 83.80; H, 6.43; N, 9.77.

10,11,12-Trimethoxydibenzo[f,h]quinazoline (8c). Yield 221 mg, 69%, white powder, mp 171-

EP

173 °С. 1H NMR (500 MHz, CDCl3) δ 10.07 (s, 1H), 9.85 (s, 1H), 8.64 (dd, J = 8.1, 1.1 Hz, 1H), 8.58 (d, J = 7.9 Hz, 1H), 7.92 (s, 1H), 7.82 (dtd, J = 14.9, 7.2, 1.2 Hz, 2H), 4.26 (s, 3H), 4.19 (s, 3H), 4.07 (s, 3H).

13

C NMR (101 MHz, CDCl3) δ 156.1, 155.7, 154.2, 153.1, 151.3, 144.4,

AC C

131.3, 129.6, 128.7, 127.9, 127.0, 123.6, 122.4, 120.8, 117.5, 100.9, 61.5, 61.4, 56.1. -Calcd. for C19H16N2O3 (320.34): C, 71.24; H, 5.03; N, 8.74. Found: C, 71.15; H, 5.05; N, 8.79. 9-Fluorodibenzo[f,h]quinazoline (8d). Yield 127 mg, 51%, white powder, mp 203-205 °С. 1H 1

H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H), 9.46 (s, 1H), 9.21 (dd, J = 8.1, 0.9 Hz, 1H), 9.15–

9.11 (m, 1H), 8.68 (dd, J = 5.7, 3.5 Hz, 1H), 7.82–7.76 (m, 2H), 7.73 (td, J = 8.0, 5.0 Hz, 1H), 7.64–7.57 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 160.9 (d, 1J = 253.2 Hz), 156.0, 153.4, 150.4, 131.3 (d, 4J = 3.6 Hz), 129.1, 128.5 (dd, 2J = 27.3, 4J = 1.4 Hz), 128.1, 128.0 (d, 3J = 10.1 Hz), 127.6 (d, 4J = 5.2 Hz), 126.8, 122.1, 121.8 (d, 3J = 8.2 Hz), 121.7, 121.4, 118.3 (d, 2J = 25.5 Hz).

17

ACCEPTED MANUSCRIPT 19

F NMR (376 MHz, CDCl3) δ 53.00 (dt, J = 14.1, 4.3 Hz, 1F). Calcd. for C16H9FN2 (248.25): C,

77.41; H, 3.65; N, 11.28. Found: C, 77.25; H, 3.49; N, 11.43. 10-Fluorodibenzo[f,h]quinazoline (8e). Yield 134 mg, 54% (for mixture of 8e and 8e'), white powder, mp 197-198 °С. Major isomer A.1H NMR (600 MHz, CDCl3) δ 9.94 (s, 1H, H-4), 9.43 (s, 1H, H-2), 9.29 (dd, J = 8.9, 6.2 Hz, 1H, H-12), 8.65 (dd, J = 6.1, 3.2 Hz, 1H, H-5), 8.51 (dd, J

and H-7), 7.47 (td, J = 8.2, 2.2 Hz, 1H, H-9).

13

RI PT

= 5.7, 3.5 Hz, 1H, H-8), 8.21 (dd, J = 10.7, 2.3 Hz, 1H, H-11), 7.76 (dd, J = 6.0, 3.0 Hz, 2H, H-6 C NMR (151 MHz, CDCl3) δ 164.88 (d, 1J =

250.8 Hz, C-10), 156.5 (C-2), 153.7 (C-4), 150.9 (C-12b), 135.53 (d, 3J = 8.8 Hz, C-8b), 129.20 (d, 4J = 3.2 Hz, C-8a), 129.0 (d, 2J = 26.2 Hz, C-6 and C-7), 128.79 (d, 3J = 9.6 Hz, C-12), 127.4 108.74 (d, 2J = 23.0 Hz, C-11).

19

SC

(C-4b), 125.6 (C-12a), 124.0 (C-8), 122.8 (C-5), 120.9 (C-4a), 116.50 (d, 2J = 22.9 Hz, C-9), F NMR (376 MHz, CDCl3) δ 55.32 (m, 1F). Calcd. for

C16H9FN2 (248.25): C, 77.41; H, 3.65; N, 11.28. Found: C, 77.63; H, 3.59; N, 11.36.

M AN U

11-Fluorodibenzo[f,h]quinazoline (8f). Yield 146 mg, 59%, white powder, mp 202-203 °С. 1H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 9.42 (s, 1H), 8.83 (dd, J = 9.9, 2.8 Hz, 1H), 8.57–8.47 (m, 3H), 7.71 (pd, J = 7.1, 1.5 Hz, 2H), 7.53 (ddd, J = 9.0, 7.8, 2.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 162.2 (d, 1J = 248.4 Hz), 155.9, 153.4, 150.3, 130.8 (d, 3J = 8.5 Hz), 129.4 (d, 4J = 1.8 Hz), 129.3, 128.9, 127.8, 126.0, 125.1 (d, 3J = 7.9 Hz), 123.3, 122.5, 121.5, 119.3 (dd, 2J = 23.5, J = 3.3 Hz), 110.9 (d, 2J = 22.8 Hz). 19F NMR (376 MHz, CDCl3) δ 49.90–49.81 (m, 1F). Calcd.

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for C16H9FN2 (248.25): C, 77.41; H, 3.65; N, 11.28. Found: C, 77.44; H, 3.57; N, 11.20. 9,11-Difluorodibenzo[f,h]quinazoline (8g). This substance was not detected in the reaction mixture by NMR 1H.

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10,12-Difluorodibenzo[f,h]quinazoline (8h). Yield 85 mg, 32%, off-white powder, mp 249-250 °С. 1H NMR (500 MHz, CDCl3) δ 10.03 (s, 1H), 9.55 (s, 1H), 8.67 (dd, J = 6.5, 2.8 Hz, 1H), 8.54 (dd, J = 6.5, 2.9 Hz, 1H), 8.16 (d, J = 10.2 Hz, 1H), 7.85–7.79 (m, 2H), 7.30–7.25 (m, 1H). C NMR (101 MHz, CDCl3) δ 163.6 (dd, 1J = 252.4, 2J = 13.7 Hz), 163.3 (dd, 1J = 267.5, 2J =

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13.1 Hz), 155.9, 153.1, 150.5 (d, 3J = 7.4 Hz), 137.2 (dd, 3J = 10.1, 4J = 2.8 Hz), 129.5, 129.3, 128.6 (t, 4J = 3.0 Hz), 127.3, 124.2, 122.6, 121.3, 114.7 (d, 4J = 2.8 Hz), 114.7 (d, 4J = 3.2 Hz), 105.3 (dd, 3J = 7.9, 4J = 1.4 Hz).

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F NMR (471 MHz, CDCl3) δ 62.57 (t, J = 12.7 Hz, 1F),

57.74–57.69 (m, 1F). Calcd. for C16H8F2N2 (266.24): C, 72.18; H, 3.03; N, 10.52. Found: C, 71.99; H, 2.89; N, 10.37. [1]Benzothieno[3,2-f]benzo[h]quinazoline (9a). Yield 192 mg, 67%, white powder, mp 248250 °С. 1H NMR (400 MHz, DMF) δ 10.79 (s, 1H), 9.75 (s, 1H), 9.55 (d, J = 8.0 Hz, 1H), 9.26 (d, J = 7.5 Hz, 1H), 8.53 (d, J = 6.4 Hz, 2H), 8.23–8.10 (m, 2H), 7.90 (dt, J = 24.7, 7.4 Hz, 2H). 18

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C NMR (101 MHz, DMF) δ 154.7, 154.1, 154.0, 150.2, 139.3, 139.1, 136.6, 131.8, 131.1,

128.8, 128.5, 126.5, 126.2, 125.9, 125.2, 124.7, 123.9, 121.8. Calcd. for C18H10N2S (286.35): C, 75.50; H, 3.52; N, 9.78. Found: C, 75.51; H, 3.36; N, 9.52. 12-Tert-butyl{[1]benzothieno[3,2-f]benzo[h]quinazoline} (9b). Yield 247 mg, 72%, white powder, mp 244-246 °С. 1H NMR (400 MHz, DMSO) δ 10.47 (s, 1H), 9.53 (s, 1H), 9.32 (d, J =

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1.9 Hz, 1H), 8.93 (d, J = 8.0 Hz, 1H), 8.24–8.18 (m, 2H), 8.09 (dd, J = 8.5, 2.1 Hz, 1H), 7.65 (ddd, J = 15.1, 14.0, 7.0 Hz, 2H), 1.52 (s, 9H). 13C NMR (101 MHz, DMSO) δ 154.8, 154.2, 151.8, 150.0, 138.9, 138.8, 136.4, 130.3, 128.8, 128.3, 126.6, 126.4, 125.3, 125.0, 124.9, 124.1, 121.7, 121.3, 35.6, 31.6. Calcd. for C22H18N2S (342.46): C, 77.16; H, 5.30; N, 8.18. Found: C,

SC

77.04; H, 5.43; N, 8.16.

10,11,12-Trimethoxy{[1]benzothieno[3,2-f]benzo[h]quinazoline} (9c). Yield 207 mg, 55%,

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white needles, mp 234-236 °С. 1H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 9.42 (s, 1H), 8.82 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 7.4 Hz, 1H), 7.63–7.54 (m, 2H), 7.24 (s, 1H), 4.07 (s, 3H), 4.00 (s, 3H), 3.94 (s, 3H). 13C NMR (101 MHz, DMSO) δ 156.6, 154.2, 154.1, 153.6, 150.0, 145.1, 138.9, 138.8, 136.2, 128.9, 126.8, 126.5, 125.5, 125.4, 124.0, 120.8, 117.0, 102.7, 61.6, 61.5, 56.8. Calcd. for C21H16N2O3S (376.43): C, 67.00; H, 4.28; N, 7.44. Found: C, 67.14; H, 4.14; N, 7.35.

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10-Fluoro{[1]benzothieno[3,2-f]benzo[h]quinazoline} (9d). Yield 85 mg, 28%, pale yellow powder, mp 264-266 °С. 1H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H), 9.48 (s, 1H), 9.16 (dd, J = 8.2, 1.0 Hz, 1H), 8.67 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 7.7 Hz, 1H), 7.78–7.71 (m, 1H), 7.67– 7.57 (m, 3H).

13

C NMR (101 MHz, CDCl3) δ 158.4 (d, J = 252.9 Hz), 153.8, 153.1 (d, J = 5.8

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Hz), 149.6 (d, J = 3.5 Hz), 140.8, 140.7, 134.5, 130.6 (d, J = 3.7 Hz), 127.9 (d, J = 8.4 Hz), 126.1, 125.6, 125.5, 124.0, 123.2 (d, J = 5.5 Hz), 121.9 (d, J = 3.3 Hz), 121.7, 116.6, 116.4. 19F NMR (376 MHz, CDCl3) δ 49.76–49.70 (m, 1F). Calcd. for C18H9FN2S (304.34): C, 71.04; H,

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2.98; N, 9.20. Found: C, 70.96; H, 3.15; N, 9.27. 11-Fluoro{[1]benzothieno[3,2-f]benzo[h]quinazoline} (9e). Yield 99 mg, 40% (for mixture of 9e and 9e'), pale yellow powder. Major isomer A. 1H NMR (600 MHz, CDCl3) δ 10.38 (s, 1H, H-4), 9.48 (s, 1H, H-2), 9.37 (dd, J = 9.0, 5.8 Hz, 1H, H-13), 8.70 (d, J = 8.2 Hz, 1H, H-5), 8.06 (d, J = 7.9 Hz, 1H, H-8), 7.79 (dd, J = 9.2, 2.3 Hz, 1H, H-12), 7.65 (t, J = 7.2 Hz, 1H, H-6), 7.58 (t, J = 7.3 Hz, 1H, H-7), 7.52 (td, J = 8.8, 2.4 Hz, 1H, H-10).13C NMR (151 MHz, CDCl3) δ 164.41 (d, 1J = 253.0 Hz, C-11), 154.6 (C-2), 153.6 (C-4), 150.1 (C-13b), 139.5 (C-8a), 138.4 (C-4a), 136.5 (C-4c), 133.0 (d, 3J = 9.8 Hz, C-13a), 129.3 (d, 3J = 9.7 Hz, C-13), 126.5 (C-7), 126.4 (C-9b), 126.0 (C-6), 125.4 (C-9a), 124.6 (C-5), 123.8 (C-8), 121.5 (C-4b), 117.1 (d, 2J = 19

ACCEPTED MANUSCRIPT 23.6 Hz, C-10), 109.7 (d, 2J = 22.9 Hz, C-12). 19F NMR (471 MHz, DMSO) δ 55.98 (td, J = 8.9, 6.0 Hz, 1F). Calcd. for C18H9FN2S (304.34): C, 71.04; H, 2.98; N, 9.20. Found: C, 70.89; H, 2.95; N, 9.07. 12-Fluoro{[1]benzothieno[3,2-f]benzo[h]quinazoline} (9f). This substance was not detected in the reaction mixture by NMR 1H. detected in the reaction mixture by NMR 1H.

(9g). This substance was not

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10,12-Difluoro{[1]benzothieno[3,2-f]benzo[h]quinazoline}

11,13-Difluoro{[1]benzothieno[3,2-f]benzo[h]quinazoline} (9h). Yield 87 mg, 27%, white powder, mp >300 °С. 1H NMR (400 MHz, CDCl3) δ 10.45 (s, 1H), 9.62 (s, 1H), 8.69 (d, J = 7.7

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Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 7.80–7.71 (m, 2H), 7.71–7.64 (m, 1H), 7.37 (ddd, J = 11.1, 8.6, 2.2 Hz, 1H). 13C NMR (151 MHz, CDCl3) δ 163.3 (d, 1J = 271.4 Hz), 163.2 (d, 1J = 271.2 Hz), 154.6, 153.4, 149.8 (d, 3J = 8.2 Hz), 139.5, 138.2 (t, 4J = 3.7 Hz), 135.9, 134.2 (dd, 2J =

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11.1, 3.7 Hz), 127.1, 126.9, 126.2, 124.8, 123.7, 121.7, 114.5 (dd, 3J = 6.0, 4J = 2.5 Hz), 106.4 (dd, 2J = 22.5, 3J = 4.4 Hz), 105.6 (t, 2J = 26.3 Hz). 19F NMR (376 MHz, CDCl3) δ 65.25–65.17 (m, 1F), 62.34–62.21 (m, 1F). Calcd. for C18H8F2N2S (322.33): C, 67.07; H, 2.50; N, 8.69. Found: C, 67.15; H, 2.38; N, 8.83.

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Acknowledgements

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The research (synthetic part) was financially supported by the Russian Science Foundation (Project No. 18-13-00409). VEV would like to acknowledge financial support for the photophysical and electrochemical studies from the Ministry of Education and Science of the Russian Federation within the framework of the State Assignment for Research (project No. АААА-А19-119012490006-1). The authors are grateful to Grigory A. Kim for carrying out the DFT calculations which were performed by using «Uran» supercomputer of the Institute of mathematic and mechanics of the Ural Brach of the Russian Academy of Sciences. NMR experiments were carried out by using equipment of the Center for Joint Use “Spectroscopy and Analysis of Organic Compounds” at the Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences.

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