Efimov 24.10.2025

1.

II Сибирский химический
симпозиум
Ефимов Илья Вагизович
АКТИВИРОВАННЫЕ ДВОЙНЫЕ СВЯЗИ В
СИНТЕЗЕ ПЯТИЧЛЕННЫХ ГЕТЕРОЦИКЛОВ
Томск
24/10/2025

2.

Introduction
2

3.

Preparation of substituted pyrroles
D. H. R. Barton, S. Z. Zard,
J. Chem. Soc. Chem. Commun.1985, 1098 – 1100;
H. Uno, M. Tanaka, T. Inoue, N. Ono, Synthesis
1999, 3, 471 – 474.
J. L. Bullington, R. R. Wolff, P. F. Jackson,
J. Org. Chem. 2002, 67, 9439 – 9442
N. C. Misra, K. Panda, H. Ila, H. Junjappa, J. Org.
Chem. 2007, 72, 1246 – 1251
3

4.

Isocyanide-enamine cycloaddition
entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
base
DBU
DBU
DBU
DBU
DBU
DBU
DBU
MeONa
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
NaH
Na2CO3
K2CO3
CsF
KOH
t-BuOK
t-BuOK
solvent
DMF
CH2Cl2
CH3OH
CF3CH2OH
CH3CN
1,4-dioxane
THF
CH3OH
1,4-dioxane
1,4-dioxane
CH3OH
CH2Cl2
CF3CH2OH
CH3CN
CH3CN
DMF
DMSO
THF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
temp., °C
25
25
25
25
25
25
25
25
25
reflux
25
25
25
25
reflux
25
25
25
25
25
25
25
25
0
0
Yield, %
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
trace
trace
trace
44
37
NR
NR
NR
NR
NR
NR
51b
68c
[a] 1 equiv. enaminone, 1 equiv. base, 1 equiv. isocyanide, 1 ml
solvent, air atmosphere; [b] 1 equiv. enaminone, 1,3 equiv. base,
1,3 equiv. isocyanide, 1 ml solvent, air atmosphere;
[c] 1 equiv. enaminone, 2 equiv. base, 2 equiv. isocyanide, 1 ml
solvent, air atmosphere;
DMF = N,N-dimethylformamide; DMSO = dimethyl sulfoxide;
THF = tetrahydrofuran.
4

5.

Synthesis of 4-aroylpyrroles
5

6.

Synthesis of 4-azolylpyrroles
Efimov, I.V., Matveeva, M.D., Luque, R., Bakulev, V.A., Voskressensky, L.G. European Journal of Organic
Chemistry. 2020. 9, 1108-1113.
6

7.

Synthesis of new BODIPY
7

8.

Synthesis of BODIPY with 1,2,4-oxadiazolyl substituents
Entry
1
Solvent
DCM
Additive
TFA
Temp (°C)
25
Base
-
Time
-
Yield (%)b
NR
2
3
4
DCM
DCE
DCE
TFA
TFA
TFA
reflux
25
reflux
Et3N
Et3N
10
days
7 days
trace
NR
trace
5
DCE
5 mol% PPTS
25
-
-
NR
6
DCE
5 mol% PPTS
reflux
-
7 days
trace
7
8
9
10
11
toluene
Solv. free
Solv. free
Solv. free
Solv. free
10% mol I2
TFA
TFA
TFA
TFA
reflux
120
150
200
120
Et3N
Et3N
Et3N
DIPEA
8 days
2h
2h
2h
2h
trace
32
17
trace
37
[a] 1 equiv. pyrrole, 0.5 equiv. aldehyde, a few drops of TFA, 1 equiv. DDQ, 10 equiv. DIPEA, 20 equiv.
BF3OEt2. [b] Isolated yield, after column chromatography.
DCM = dichloromethane; DCE = 1,2-dichloroethane; TFA = trifluoroacetic acid; PPTS = pyridinium ptoluenesulfonate; DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; DIPEA = N,N-diisopropylethylamine;
NR = no reaction.
8

9.

Scope of new BODIPY with 1,2,4-oxadiazolyl substituents
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
Aldehyde
Benzaldehyde
ortho-tolualdehyde
para-tolualdehyde
meta-anisaldehyde
para-anisaldehyde
ortho-bromobenzaldehyde
para-bromobenzaldehyde
para-chlorobenzaldehyde
meta-fluorobenzaldehyde
para-fluorobenzaldehyde
meta-nitrobenzaldehyde
para-nitrobenzaldehyde
meta-(trifluoromethyl)benzaldehyde
Product
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
Yield (%)b
37
30
43
41
56
29
16
29
31
24
0
0
0
14
15
16
3,4-dimethoxybenzaldehyde
2,5-dimethoxybenzaldehyde
2,6-dichlorobenzaldehyde
8n
8o
8p
0
0
0
[a] 1 equiv. pyrrole, 0.5 equiv. aldehyde, a few drops of TFA, 1 equiv. DDQ, 10 equiv. DIPEA, 20 equiv. BF 3OEt2. [b] Isolated yield.
9

10.

Excitation and Emission Spectra in Various Solvents
Fig. 1 Excitation (black lines) and emission (red lines) spectra
of the 8a compound in four different solvents.
The solvents and the measured quantum yield (QY) values are
shown in the graph legend
Fig. 2 Structures of 8a and 1,3,5,7,8-pentaphenyl BODIPY 9
10

11.

11
Results of photophysical experiments
Values of the photoluminescence quantum yield for studied compounds in different solvents
Solvent
C6H12 (ε 2.0)a
CH2Cl2 (ε 9.1)
MeOH (ε 33)
MeCN (ε 36)
Entry
Compound
λex,
nm
λem,
nm
Stokes
shift, nm
QYb
λex, nm
λem,
nm
Stokes
shift, nm
QY
λex,
nm
λem,
nm
Stokes
shift, nm
QY
λex, nm
λem,
nm
Stokes
shift, nm
QY
1
8a
584
620
36
57.2%
588
629
41
80.1%
580
623
43
53.8%
576
621
45
63.2%
2
8b
584
620
36
40.1%
583
620
37
59.5%
581
622
41
79.4%
576
621
45
68.1%
3
8c
578
614
36
66.6%
581
623
42
84.6%
579
620
41
72.9%
574
618
44
54.3%
4
8d
583
620
37
<1%c
584
626
42
22.8%
582
621
39
13.7%
579
618
39
3.0%
5
8e
591
614
23
<1%
581
621
40
53.2%
581
619
38
6.3%
574
641
67
1.2%
6
8f
596
633
37
87.5%
595
639
44
75.9%
592
635
43
92.0%
588
634
46
71.9%
7
8g
586
626
40
19.5%
586
630
44
37.2%
583
626
43
37.1%
582
625
43
83.6%
8
8h
587
622
35
45.9%
587
628
41
23.6%
585
624
39
45.2%
581
624
43
42.6%
9
8i
588
625
37
47.4%
590
632
42
44.7%
587
627
40
71.4%
582
626
44
80.4%
10
8j
587
621
34
32.2%
587
628
41
35.3%
583
624
41
91.5%
580
622
42
40.2%
[a] The solvent dielectric constant. [b] Absolute QY, measured using the integrated sphere. [c] The quantum yield in some cases was too small to be estimated precisely.

12.

Quantum chemical calculations
The energies for HOMO and LUMO of investigated derivatives;
Shapes of frontier orbitals for 8a calculated at B3LYP/6-31G(d)/CPCM(DCM).
Entry
Compound
HOMO/eV
LUMO/eV
1
8a
-5.74
-3.24
2
8b
-5.74
-3.24
3
8c
-5.73
-3.22
4
8d
-5.72
-3.24
5
8e
-5.72
-3.20
6
8f
-5.76
-3.34
7
8g
-5.78
-3.31
8
8h
-5.77
-3.33
9
8i
10
8j
-5.76
-5.76
-3.30
-3.28
HOMO of 8a.
LUMO of 8a.
M. Matveeva, D. Zhilyaev, A. Miftyakhova, P. Chulkin, P. Janasik, L. Voskressensky, G. Talarico and I. Efimov . New J. Chem., 2022,
46, 5725-5729.
12

13.

Synthesis of new BODIPY with aroyl substituents
entry
1
2
3
4
5
6
7
8
solvent
DCM
TCE
Toluene
DMF
DMF
No solvent
DCM
DCM
additives
TFA
TFA
p-TSA
TFA
TFA
TFA
TFA, POCl3
POCl3
temp., °C
25
87
110
25
153
Melt
25
25
Yield, %
NR
NR
NR
NR
NR
Decomp.
92%a
NR
[a]2 equiv. pyrrole, 1,1 equiv. aldehyde, 0,5 ml
TFA, air atmosphere;
DCM = dichloromethane; TCE =
trichloroethylene; DMF = N,Ndimethylformamide; TFA = trifluoroacetic acid,
DDQ = 2,3-dichloro-5,6-dicyano-1,4benzoquinone, DIPEA = N,Ndiisopropylethylamine.
13

14.

Scope of new BODIPY with aroyl substituents
14
Total yield 23-45%
X-Ray structure of BODIPY 12c

15.

Results of photophysical experiments
Photophysical properties in DCM
Compound
maxλ , [nm]
abs
ε·104, [M-1cm-1]
λex, [nm]
max λ , [nm]
em
Stokes shift, [eV]
Stokes shift [cm-1]
Quantum yield, %
12a
567
5,08
569
617
0.17
1370
83
12b
565
6,80
567
618
0.18
1450
84
12c
566
3,26
569
620
0.18
1450
96
12d
568
4,06
570
620
0.18
1450
71
12e
571
3,70
572
634
0.21
1690
83
12f
563
6,75
567
614
0.17
1370
67
12g
561
5,11
564
616
0.19
1530
93
12h
562
4,74
566
610
0.16
1290
12
12i
567
5,32
571
619
0.17
1370
40
12j
570
5,74
574
622
0.17
1370
84
12k
570
5,68
572
623
0.18
1450
85
12l
570
5,98
571
624
0.18
1450
85
12m
566; 267
4,49; 4,49
567
617
0.18
1450
84
12n
565
3,71
567
617
0.18
1450
94
I. V. Efimov, A. R. Miftyakhova, M. D. Matveeva, D. I. Zhilyaev, P. Czulkin, P. Janasik, G. Talarico
and L. G. Voskressensky. New J. Chem., 2022, 46, 19291.
15

16.

Scope of new BODIPY with isoxazolyl substituents
Entry
Aldehyde
Product
Yield (%)b
1 Benzaldehyde
15a
32
2 ortho-tolualdehyde
15b
35
3 meta-anisaldehyde
15c
43
4 ortho-bromobenzaldehyde
15d
25
5 para-chlorobenzaldehyde
15f
35
[a] 1 equiv. pyrrole, 0.5 equiv. aldehyde, a few drops of TFA, 1 equiv. DDQ, 10 equiv. DIPEA, 20 equiv. BF3OEt2. [b]
Isolated yield.
16

17.

Results of photophysical experiments
UV-Vis-NIR
Compound
maxλ
а
abs
[nm]
Photoluminescence
Eoptg [eV]
ε·104, [M1cm-1] λex [nm]
max λ
а
em [nm]
Stokes
[eV]
shift Quantum
yield, Φfl
15a
577
2.01
6.51±0,2
540; 550; 560
619
0.15
0.86b
15b
577
2.00
3.28±0,2
540; 550; 560
620
0.15
0.87b
15c
578
2.01
5.06±0,8
540; 550; 560
619
0.14
0.98c
15d
585
1.98
1.82±0,1
540; 550; 560
625
0.14
0.82с
15e
580
2.00
4.57±0,7
540; 550; 560
621
0.14
0.92c
a Maxima obtained from deconvolution of the spectra; b Quantum yield determined relative to cresyl violet standard in
EtOH (Фf=0,56); c
Matveeva, M. D., Zheleznova, T. Y., Kostyuchenko, A. S., Miftyakhova, A. R., Zhilyaev, D. I., Voskressensky, L. G., Talarico, G.,
Efimov, I. V. ChemistrySelect, 2023, 8, e202204465.
17

18.

Comparison of absorption and emission maxima for
BODIPY with various substituents
18

19.

Representative biologically active compounds having 6-azaindole and
pyrrolo[3,2-d]pyridazine moiety
Application:
Antiviral
Antibacterial
Anticancer
Antiasthma activity
19

20.

Synthesis of pyrrolo[2,3-d]pyridazines and pyrrolo[2,3-c]pyridines
(6-azaindoles) from pyrrolo-2,3-dicarbonyles
20

21.

Synthesis of pyrrolo-2,3-dicarbonyles
Table. Substrate scope with respect to Ar1 and Ar2
№
1
2
3
4
5
6
7
8
9
10
Product
16a
16b
16c
16d
16e
16f
16g
16h
16i
16j
Ar1
Ph
4-FC6H4
4-ClC6H4
2-Naphthyl
Ph
4-FC6H4
4-ClC6H4
2-ClC6H4
Ph
2-Naphthyl
Ar2
Ph
Ph
Ph
Ph
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CH3C6H4
4-CH3C6H4
Yield, %
40
54
90
44
44
54
36
52
53
36
21

22.

Synthesis of 2,4-substituted pyrrolo[2,3-d]pyridazines
Table. Scope of substrates for synthesis of 2,4-substituted pyrrolo[2,3-d]pyridazines
№
Product
Ar1
Ar2
reaction
time, h
Yield, %
1
17a
Ph
Ph
12
44
2
17b
4-FC6H4
Ph
12
52
3
17c
4-ClC6H4
Ph
12
48
4
17d
4-FC6H4
4-OMe-C6H4
12
33
22

23.

Synthesis of pyrrolo[2,3-d]pyridazin-5-ium chlorides
Table. Scope of the pyrrolo[2,3-d]pyridazin-5-ium chlorides 18a-k.
23
№
1
2
3
4
5
6
Product
18a
18a’
18b
18c
18d
18e
Ar1
Ph
Ph
4-FC6H4
4-ClC6H4
Naphthyl
Ph
Ar2
Ph
Ph
Ph
Ph
Ph
4-OMe-C6H4
R
Ph
Ph
Ph
Ph
Ph
Ph
Yield, %
64
76
74
70
89
85
7
18f
4-FC6H4
4-OMe-C6H4
Ph
81
8
9
18g+19
18h
4-ClC6H4
2-ClC6H4
4-OMe-C6H4
4-OMe-C6H4
Ph
Ph
12 (18g)+66 (19)
78
10
11
12
18i
18j
18k
4-FC6H4
Ph
Naphthyl
4-OMe-C6H4
4-Me-C6H4
4-Me-C6H4
4-CH3SO2C6H4
Ph
Ph
65
98
54

24.

Synthesis of the 6-azaindoles
Scope of the tested aromatic amines
and reaction conditions
Table 4. Scope of the
6-azaindoles 21a-e.
24
№
1
2
3
4
5
6
Product
21a
21b
21c
21d
21e
21f
Conditions
TEA, ethanol
TEA, ethanol
TEA, ethanol
TEA, ethanol
TEA, ethanol
TEA, ethanol
Ar1
4-FC6H4
Ph
4-FC6H4
4-ClC6H4
Ph
2-Naphtyl
№
1
Amine
benzylamine
Base
-
Conditions
DCE
2
benzylamine
TEA
DCE
3
benzylamine
TEA
4
4-Bromobenzylamine
TEA
5
4-Bromobenzylamine
DBU
C2H5OH
rt-> reflux,
ethanol
rt-> reflux,
ethanol
Ar2
Ph
4-OMe-C6H4
4-OMe-C6H4
4-OMe-C6H4
4-Me-C6H4
4-Me-C6H4
Yield, %
46
70
87
94
63
99
Yield
no
reaction
no
reaction
no
reaction
no
reaction
no
reaction

25.

Relative Gibbs free energy profiles and optimized structures of the
reaction of pyrrolo-2,3-dicarbonyl 16a with phenyl hydrazine
25

26.

Relative Gibbs free energy profiles and optimized structures of the
reaction of pyrrolo-2,3-dicarbonyl 16f with glycine methyl ester
26

27.

Proposed mechanism of the formation 6-azaindoles
Scheme 6. Proposed mechanism of the formation 6-azaindoles 21a-e.
Efimov, I.V., Sultanova, Y.V., Cicolella, A., Talarico, G., Voskressensky, L.G.. Organic and Biomolecular
Chemistry, 2024, 22(31), 6331–6341.
27

28.

Results of photophysical experiments for 6azaindoles with various substituents
Normalized absorbance
1,0
0,8
0,6
0,4
0,2
0,0
300
350
400
Wavelenght (nm)
450
500
6a
6b
6c
6d
6e
6f
1,0
Normalized Emission Intensity
6a
6b
6c
6d
6e
6f
0,8
0,6
0,4
0,2
0,0
350
400
450
500
550
600
Wavelenght (nm)
Figure. Normalized (left) absorption and (right) luminescence spectra of the compounds 21a−e in the DMF.
28

29.

Results of photophysical experiments for 6azaindoles with various substituents
Table. Photophysical data for 6-azaindolesa
Compounds
Absorbance, λmax
(nm)
Emissionb,
λmax (nm)
Stokes
shift, (eV)
−1
e (M
−1
cm )
Quantum
yield, (Φ)c
21a
21b
21c
21d
21e
21f
346
348
349
340
342
347
415
416
416
404
407
414
0.596
0.582
0.572
0.578
0.579
0.578
7939
11736
34627
11904
14150
11091
0.94
0.94
0.72
0.77
0.83
0.88
a Measured in DMF (c = 10−5 M) at 298 K. b Excited at 310 nm. c Measured with quinine sulphate in 0.1 N H SO as the standard.
2
4
29

30.

Synthesis of 5-(Trichloromethyl)-Isoxazolines
30

31.

Optimization of reaction conditions
№
Solvent
Temp.
Time, h
Base
Yield of 24b, %
24b/25, %d
1
1,4-dioxane
rt
36
TEA
41
75/25
2
3
4
5
6
7
8
9
10
11
12
13
14
1,4-dioxane
DMF
DMF
CH3OHa
CH3OHb
CH3OHc
CH3OHc
EtOAc
THF
CH3OHc
CH3OHc
CH3OHc
CH3OHc
bp
rt
bp
rt
rt
rt
bp
rt
rt
rt
rt
rt
rt
6
24
6
20
20
20
20
72
48
20
20
20
20
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
K2CO3
DIPEA
DBU
DABCO
35
52
57
48
54
63
61
42
48
5
55
27
49
77/23
75/25
73/27
100/0
100/0
100/0
100/0
71/29
73/27
100/0
100/0
100/0
100/0
Ar = 4-CH3OC6H4; TEA = triethylamine; a Reaction conditions: 1a (0.1 mmol), 2d (0.1 mmol), solvent (3.0 mL), and base (0.1 mmol); b
Reaction conditions: 1a (0.1 mmol), 2d (0.15 mmol), solvent (3.0 mL), and base (0.15 mmol); c Reaction conditions: 1a (0.1 mmol), 2d
(0.2 mmol), solvent (3.0 mL), and base (0.2 mmol); d Product ratio (3b/4) determined after column chromatography.
31

32.

Scope of the synthesized 5-(CCl3)-isoxazolines
X-Ray structure of 5-CCl3-isoxazoline 24c.
32

33.

Reaction mechanism
DFT mechanism of isoxazoline formation starting from hydroxamoyl chloride and CCl 3enone. Reported Gibbs energies in kcal/mol referenced to 2a.
I.V. Efimov, V. A. Sokolov, A. V. Vasilyev, Y. Kumar, Khushal, M. C. D’Alterio, G. Talarico and L. G. Voskressensky.
New J. Chem., 2025, 49, 17987 - 17996
33

34.

Выводы
1. Разработан новый метод синтеза 2,4-дизамещенных пирролов;
2. Разработаны методы синтеза и исследованы фотофизические свойства новых BODIPY, содержащих
оксадиазольный, изоксазольный либо ароильный заместители в 1 и 7 положениях;
3. Разработаны методы синтеза и исследованы фотофизические свойства пирроло[2,3-d]пиридазинов и
пирроло[2,3-с]пиридинов (6-азаиндолов);
4. Разработан новый метод синтеза CCl3-изоксазолинов
34

35.

Acknowledgments
1. This work was prepared with financial support by the RSF, RFBR and RUDN University Strategic Academic
Leadership Program.
2. Dr. Giovanni Talarico, Massimo C. D’Alterio and Alessadra Cicolella, Università degli Studi di Napoli Federico II, Napoli,
Italy
3. Prof. Dr. Leonid G. Voskressensky, Dr. Maria Matveeva and Dr. Almira Miftyakhova, RUDN University, Moscow, Russia
4. Dr. Pavel Chulkin and Patric Janasik, Silesian University of Technology, Glivice, Poland
5. Dr. Anastacia S. Kostyuchenko and Tatiana Yu. Zheleznova, Omsk State Technical University, Omsk, Russia
6. Vladislav Sokolov and Prof. Dr. Alexander V. Vasil’ev, Saint Petersburg State University, Saint Petersburg, Russia
Thank you for attention!