Synthesis of formyl and carboxy derivatives of heterocycles by modification of 2-(2-aminovinyl)- benzofuran-5,6-dicarbonitriles

Article abstract of DOI:10.1134/S1070428016090074

Procedures have been developed for the synthesis of 2-formylbenzofuran-5,6-dicarbonitriles, 5,6-dicyanobenzofuran-2-carboxylic acids, and formyldibenzo[b,d]furan-2,3-dicarbonitriles by modification of 2-(2-aminovinyl)benzofuran-5,6-dicarbonitriles with so

Full text of DOI:10.1134/S1070428016090074

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 9, pp. 1297–1303. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © Zh.V. Chirkova, S.I. Filimonov, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 9, pp. 1309–1315.
Synthesis of Formyl and Carboxy Derivatives
of Heterocycles by Modification of 2-(2-Aminovinyl)-
benzofuran-5,6-dicarbonitriles
Zh. V. Chirkova* and S. I. Filimonov
Yaroslavl State Technical University, Moskovskii pr. 88, Yaroslavl, 150023 Russia
*e-mail: chirkovazhv@ystu.ru
Received April 15, 2016
Abstract—Procedures have been developed for the synthesis of 2-formylbenzofuran-5,6-dicarbonitriles,
5,6-dicyanobenzofuran-2-carboxylic acids, and formyldibenzo[b,d]furan-2,3-dicarbonitriles by modification of
2-(2-aminovinyl)benzofuran-5,6-dicarbonitriles with sodium periodate or Vilsmeier reagent.
DOI: 10.1134/S1070428016090074
Synthesis of various substituted 2-formylbenzofu-
rans and benzofuran-2-carboxylic acids is a promising
line of development of heterocyclic chemistry. Interest
in compounds of these series is determined by their
diverse pharmacological activity, in particular anti-
tumor [1, 2] and anti-inflammatory activity [3], as well
as selective cytotoxicity against cancer cells [4].
low as ~2%. Therefore, it was proposed to oxidize
preliminarily prepared 2-(2-aminovinyl)benzofuran-
5,6-dicarbonitriles [16] with sodium periodate [17, 18].
2-[2-(Dimethylamino)ethenyl]benzofuran-5,6-di-
carbonitriles 2a–2d were synthesized from the corre-
sponding 2-methylbenzofurans 1a–1d [15] according
to the procedure described in [16]. The reaction of
3-acetyl-2-methylbenzofuran-5,6-dicarbonitrile (1a)
with dimethylformamide dimethyl acetal (DMF-DMA)
at ~80°C involved only the 2-methyl group which is
a stronger CH acid than the 3-acetyl methyl group; as
a result, compound 2a was selectively formed. Its
structure was confirmed by NMR (including NOESY
data) and mass spectra.
A general procedure for the synthesis of 2-formyl-
benzofurans is based on the oxidation of methyl group
in the 2-position with SeO2 [5–7]; another procedure
involves radical oxidation of substituted vinyloxyben-
zenes with atmospheric oxygen in the presence of
metal-free catalysts [8]. Various substituted benzo-
furan-2-carboxylic acids were synthesized by conden-
sation of salicylaldehyde or its derivatives with chloro-
acetic acid [9, 10] or 1,1-dichloroethene [11] and
by base-catalyzed ring contraction of substituted
3-bromocoumarins [12]. For preparative purposes,
substituted benzofuran-2-carboxylic acids are obtained
in two steps: in the first step, substituted 2-methyl-
benzofuran is oxidized with SeO2 to benzofuran-
2-carbaldehyde, and the aldehyde group in the latter is
then converted into carboxy by the action of various
oxidants [7, 13, 14].
Dimethylaminovinyl derivatives 2a–2d [17] were
oxidized with NaIO4 in 50% aqueous THF at 50–60°C
(5–6 h). The products were mixtures of 2-formyl-
benzofuran-5,6-dicarbonitriles 3a–3d and 5,6-dicyano-
benzofuran-2-carboxylic acids 4b–4d. Formyl deriva-
tives 3a–3d were extracted into methylene chloride,
and the extract was washed with aqueous sodium
hydrogen carbonate. Carboxylic acids 4b–4d were
isolated by acidification of the aqueous solution with
HCl. The overall yield was 55–70%. Acid 4a was not
isolated, presumably due to stability of aldehyde 3a to
further oxidation (Scheme 1).
We have developed methods for the synthesis of
new substituted formylbenzofuran-5,6-dicarbonitriles
and 5,6-dicyanobenzofuran-2-carboxylic acids. The
oxidation of 2-methylbenzofuran-5,6-dicarbonitriles
[15] with SeO2 was too slow. According to the
1H NMR data, the substrate conversion in 100 h after
the reaction started (in dioxane under reflux) was as
The yields of 3a–3d and 4b–4d and their ratio
depended primarily on the reaction temperature and, to
a lesser extent, on the R substituent. No oxidation was
observed below 40°C, whereas raising the temperature
above 60°C resulted in considerable tarring and forma-
1297

CHIRKOVA, FILIMONOV
1298
Scheme 1.
O
O
R
R
Me
Me
NC
NC
NC
N
(MeO)2CHNMe2
Me
O
O
NC
1a–1d
2a–2d
O
R
O
R
NC
NC
NaIO4
+
CHO
COOH
O
O
NC
NC
3a–3d
4b–4d
R = Me (a), EtO (b), Ph (c), 4-MeC6H4 (d).
tion of products which were difficult to identify. The
yield of acids 4 increased as the amount of the oxidant
increased; however, we failed to find conditions for the
selective formation of either aldehyde 3b–3d or car-
boxylic acid 4b–4d. Presumably, the oxidation to alde-
hyde 3 is the rate-determining step; since aldehydes
readily undergo further oxidation, the yield of 3
considerably decreases, while the corresponding acid
accumulates in the reaction mixture.
formation of the corresponding formyl derivatives
[19, 20]. In addition, aldehydes can be obtained by
acid hydrolysis of the dimethylaminovinyl fragment
of 2 [21, 22].
Benzofuran-5,6-dicarbonitriles 2c–2f with an aro-
matic or heterocyclic R substituent reacted with
POCl3/DMF at 80–90°C to give previously unknown
formylvinyl derivatives 5c–5f (Scheme 2). A probable
mechanism for the formation of structurally related
compounds was described in [23, 24].
The structure of 3a–3d and 4b–4d was confirmed
by IR, NMR, and mass spectra. The IR spectra of 3a–
3d characteristically contained an absorption band at
1670–1680 cm–1, which is typical of aldehyde car-
The structure of 5c–5f was determined using
different two-dimensional (1H–13C) NMR techniques
13
and high resolution mass spectrometry. The C NMR
1
bonyl. The aldehyde proton resonated in the H NMR
spectrum of 5e contained two carbonyl carbon signals.
Analysis of the NOESY, HMBC, and HSQC spectra of
5e showed that the formyl group is attached to the
α-carbon atom with respect to the furan ring and that
the exocyclic double bond in molecule 5e has exclu-
sively E configuration. This follows from the NOESY
cross peaks between the N-methyl protons, on the one
hand, and aldehyde proton and proton at the double
bond, on the other (see below). Such configuration of
molecule 5e favors intramolecular hydrogen bonding
between the aldehyde proton and nitrogen atom of the
aminovinyl fragment; as a result, the aldehyde proton
signal is broadened.
spectra of 3a–3d at δ 9.74–10.35 ppm. No COOH
proton signal was generally observed in the H NMR
1
spectra of acids 4b–4d because of exchange with the
solvent. The presence of a carboxy group in 4c was
13
confirmed by the C NMR spectrum which displayed
downfield signals of the acid carbonyl carbon atom at
δC 158.5 ppm and ketone carbonyl at δC 188.6 ppm.
Alternatively, an aldehyde group can be introduced
into molecules of aromatic and heterocyclic com-
pounds by the Vilsmeier–Haack reaction. Treatment of
compounds containing a methyl group with a mixture
of DMF and phosphoryl chloride (POCl3) leads to the
Scheme 2.
O
O
R
R
Me
Me
POCl3, DMF
NC
NC
NC
NC
N
CHO
O
O
Me2N
2c–2f
5c–5f
R = Ph (c), 4-MeC6H4 (d), 4-MeOC6H4 (e), thiophen-2-yl (f).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 9 2016

SYNTHESIS OF FORMYL AND CARBOXY DERIVATIVES
1299
MeO
The structure of 6 and 7 was confirmed by IR,
NMR, and mass spectra. The structure of 6 was unam-
biguously determined by analysis of two-dimensional
1H–13C correlation spectra (HSQC, HMBC). Other
possible structures were ruled out by the presence of
strong C4a/1-H and C5a/7-H strong peaks, as well as of
weak C5a/CHO correlation.
O
H
Me
Me
NC
NC
N
H
O
O
Cl
8
9
5e
1
7
NC
NC
9a
2
3
9b
4a
5a
6
Compound 2a reacted with 3 equiv of Vilsmeier
reagent in a different way (Scheme 3). Apart from the
2-methyl group, the reaction at 40–90°C involved the
3-acetyl group of 2a and afforded a mixture of mono-
and diformyldibenzo[b,d]furan-2,3-dicarbonitriles 6
and 7, the former prevailing. When the reaction was
carried out at room temperature, compound 6 was
isolated as the major product. Likewise, the reaction of
1a with Vilsmeier reagent gave a mixture of 6 and 7.
The product ratio depended on the amount of
Vilsmeier reagent, temperature, and reaction time.
Increase of the amount of POCl3 to 10 equiv, tempera-
ture to 90°C, and reaction time to 6 h favored forma-
tion of dialdehyde 7 whose yield attained 50%. How-
ever, we failed to find conditions for the selective
formation of 7. Aldehyde 6 was converted into hy-
drazone 8 by treatment with hydrazine hydrate and
reduced to alcohol 9 with NaBH4 (Scheme 4).
H
O
4
O
6
The formation of dibenzofurancarbaldehydes 6 and
7 from substituted benzofurans is the most remarkable
result of our experiments since compounds of this sort
are commonly synthesized by formylation of prelimi-
narily prepared dibenzofurans [25], oxidation of hy-
droxymethyl-substituted dibenzofurans [26], or intra-
molecular cyclization of phenols containing a formyl
group [27, 28].
Scheme 5 shows a probable mechanism of forma-
tion of compounds 6 and 7. 3-Acetyl-2-methylbenzo-
furan-5,6-dicarbonitrile (1a) reacts with POCl3/DMF
to give dimethylaminovinyl derivative 2a. Further re-
action of 2a with Vilsmeier reagent leads to diamino-
vinyl intermediate A. Analogous intermediate derived
Scheme 3.
O
Me
NC
NC
Me
O
CHO
Cl
Cl
1a
POCl3, DMF
NC
NC
NC
NC
+
(MeO)2CHNMe2
DMF
CHO
CHO
O
O
O
Me
Me
6
7
NC
NC
N
Me
O
2a
Scheme 4.
Cl
Cl
Cl
NC
NC
NC
NC
NC
NNH2
CHO
CH2OH
O
O
O
NC
8
6
9
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 9 2016

CHIRKOVA, FILIMONOV
1300
Scheme 5.
O
O
O
Me
Me
Me
Me
N
Me
Me
POCl3, DMF
POCl3, DMF
NC
NC
NC
NC
NC
NC
N
N
Me
Me
O
O
O
Me
Me
1a
2a
A
O
Cl
Cl
H+
POCl3, DMF
NaHCO3
NC
NC
NC
NC
NC
NC
–Me2NH
CHO
O
O
O
Me2N
Me2N
B
C
6
Me2N
NMe2
O
O
Me
N
H+
POCl3, DMF
NC
NC
NC
NC
–Me2NH
Me
O
O
Me2N
Me
N
Me
D
E
NMe2
CHO
Cl
Cl
POCl3, DMF
NaHCO3
NC
NC
NC
NC
CHO
O
O
Me2N
F
7
from 2c–2f is then converted into aldehydes 5c–5f. In
the reactions with 1a (2a), the subsequent transforma-
tions of intermediate A follow two pathways. The first
pathway involves intramolecular cyclization to dihy-
drodibenzofuran structure B with elimination of di-
methylamine, replacement of the carbonyl oxygen
atom by chlorine, and hydrolysis of intermediate C to
aldehyde 6 with aqueous sodium hydrogen carbonate.
Alternatively, further reaction of A with Vilsmeier
reagent at the acetyl group leads to intermediate D
whose cyclization to dihydrodibenzofuran E is fol-
lowed (as in the first pathway) by aromatization and
chlorination with formation of intermediate F as pre-
cursor to dicarbaldehyde 7.
at 30°C using DMSO-d6 as solvent and reference
(DMSO-d5, δ 2.50 ppm; DMSO-d6, δC 39.5 ppm).
The two-dimensional NMR spectra were recorded
using Bruker standard pulse sequences; NOESY mix-
ing time 0.3 s.
The mass spectra were taken on a Finnigan MAT
INCOS 50 mass spectrometer coupled with a gas
chromatograph and on a Kratos MS-30 high-resolution
mass spectrometer (UK); electron impact, 70 eV; ion
source temperature 100–220°C. The NMR and mass
spectral studies were performed at the Zelinskii
Institute of Organic Chemistry, Russian Academy of
Sciences (Moscow, Russia).
The elemental analyses were obtained on a Perkin
Elmer 2400 analyzer at the Analytical Laboratory
(Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, Moscow, Russia). The
melting points were determined using a DSK-5500
differential scanning calorimeter or a Büchi M-560
melting (boiling) point apparatus.
EXPERIMENTAL
The IR spectra (700–4000 cm–1) were recorded in
mineral oil on a Perkin Elmer RX-1 spectrometer with
Fourier transform. The NMR spectra were measured
on a Bruker DRX-400 or Bruker DRX-500 instrument
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 9 2016

SYNTHESIS OF FORMYL AND CARBOXY DERIVATIVES
1301
2-Formyl-3-(4-methylbenzoyl)-1-benzofuran-5,6-
dicarbonitrile (3d). Yield 0.21 g (34%), mp 215–
217°C. IR spectrum, ν, cm–1: 2237 (CN), 1679 (C=O),
Compounds 3a–3d and 4b–4d (general proce-
dure). Compound 2a–2d, 2 mmol, was dissolved in
5 mL of 50% aqueous THF, 1.5 g (7 mmol) of NaIO4
was added, and the mixture was stirred for 5–6 h at
50–60°C (TLC). The mixture was cooled, 20 mL of
10% aqueous sodium hydrogen carbonate was added,
the mixture was extracted with methylene chloride, the
extract was subjected to silica gel chromatography, the
eluate was evaporated, and the precipitate was filtered
off and dried. We thus isolated compounds 3a–3d. The
aqueous phase obtained after extraction was acidified
to pH 2–3 with aqueous HCl, and the precipitate of
4b–4d was filtered off, washed with water, and dried.
1
1650 (C=O), 1598 (C=C), 1290 (C–O–C). H NMR
spectrum, δ, ppm: 2.44 s (3H, CH3), 7.41 d (2H, o-H,
J = 8.1 Hz), 7.87 d (2H, m-H, J = 8.1 Hz), 8.49 s (1H,
7-H), 8.93 s (1H, 4-H), 9.76 s (1H, CHO). Mass spec-
trum, m/z (Irel, %): 314 (43) [M]+, 271 (13), 195 (9),
139 (34), 119 (14), 91 (100), 65 (70). Found, %:
C 72.43; H 3.19; N 8.89. C19H10N2O3. Calculated, %:
C 72.61; H 3.21; N 8.91. M 314.30.
5,6-Dicyano-3-(ethoxycarbonyl)-1-benzofuran-2-
carboxylic acid (4b). Yield 0.20 g (35%), mp 244–
1
246°C. H NMR spectrum, δ, ppm: 1.12 t (3H, CH3,
3-Acetyl-2-formyl-1-benzofuran-5,6-dicarbo-
nitrile (3a). Yield 0.081 g (17%), mp 170–171°C. IR
spectrum, ν, cm–1: 2231 (CN), 1680 (C=O), 1604
J = 7.0 Hz), 4.17 q (2H, CH2, J = 7.0 Hz), 8.69 s (1H,
7-H), 8.79 s (1H, 4-H); no OH proton signal was
observed because of exchange. Found, %: C 59.03;
H 2.81; N 9.84. C14H8N2O5. Calculated, %: C 59.16;
H 2.84; N 9.86.
1
(C=C), 1280 (C–O–C). H NMR spectrum, δ, ppm:
2.87 s (3H, CH3), 8.87 s (1H, 7-H), 8.93 s (1H, 4-H),
10.25 s (1H, CHO). 13C NMR spectrum, δC, ppm:
31.60 (Me), 110.89, 113.36, 115.66 (CN), 115.79
(CN), 119.93, 125.20, 128.89, 153.71, 154.70, 167.07,
181.04 (CHO), 193.22 (C=O). Mass spectrum, m/z
(Irel, %): 238 (37) [M]+, 195 (100), 43 (35). Found, %:
C 65.39; H 2.43; N 11.74. C13H6N2O3. Calculated, %:
C 65.55; H 2.54; N 11.76. M 238.20.
3-Benzoyl-5,6-dicyano-1-benzofuran-2-carbox-
ylic acid (4c). Yield 0.19 g (30%), mp 210–212°C. IR
spectrum, ν, cm–1: 3505 (OH), 2237 (CN), 1724
(C=O), 1641 (C=O), 1597 (C=C), 1278 (C–O–C).
1H NMR spectrum, δ, ppm: 7.55 t (2H, o-H, J =
7.5 Hz), 7.72 t (1H, p-H, J = 7.5 Hz), 7.91 d (2H, m-H,
J = 7.5 Hz), 8.56 s (1H, 7-H), 8.88 s (1H, 4-H); no OH
proton signal was observed because of exchange.
13C NMR spectrum, δC, ppm: 110.4, 112.8, 115.8,
116.0, 119.9, 124.3, 129.0, 129.3, 129.6, 130.3, 134.5,
136.3, 147.9, 154.1, 158.5, 188.6. Mass spectrum, m/z
(Irel, %): 316 (100) [M]+, 272 (30), 271 (34), 244 (60),
239 (49), 105 (38), 77 (35). Found, %: C 68.18;
H 2.50; N 8.81. C18H8N2O4. Calculated, %: C 68.36;
H 2.55; N 8.86. M 316.28.
Ethyl 5,6-dicyano-2-formyl-1-benzofuran-3-car-
boxylate (3b). Yield 0.11 g (20%), mp 234–236°C. IR
spectrum, ν, cm–1: 2235 (CN), 1712 (C=O), 1681
1
(C=O), 1600 (C=C), 1287 (C–O–C). H NMR spec-
trum, δ, ppm: 1.43 t (3H, CH3, J = 7.1 Hz), 4.50 q (2H,
CH2, J = 7.1 Hz), 8.80 s (1H, 7-H), 8.90 s (1H, 4-H),
10.37 s (1H, CHO). Mass spectrum, m/z (Irel, %): 268
(20) [M]+, 254 (14), 239 (33) [M – COH]+, 226 (25),
223 (21), 212 (64), 195 (98) [M – COOEt]+, 168 (44),
139 (100), 88 (26), 87 (30). Found, %: C 62.42;
H 2.96; N 10.41. C14H8N2O4. Calculated, %: C 62.69;
H 3.01; N 10.44. M 268.23.
5,6-Dicyano-3-(4-methylbenzoyl)-1-benzofuran-
2-carboxylic acid (4d). Yield 0.22 g (34%), mp 219–
221°C. IR spectrum, ν, cm–1: 3513 (OH), 2223 (CN),
1728 (C=O), 1638 (C=O), 1603 (C=C), 1286
1
(C–O–C). H NMR spectrum, δ, ppm: 2.40 s (3H,
3-Benzoyl-2-formyl-1-bezofuran-5,6-dicarbo-
nitrile (3c). Yield 0.22 g (36%), mp 216–218°C. IR
spectrum, ν, cm–1: 2238 (CN), 1677 (C=O), 1655
CH3), 7.35 d (2H, o-H, J = 8.1 Hz), 7.81 d (2H, m-H,
J = 8.1 Hz), 8.51 s (1H, 7-H), 8.87 s (1H, 4-H); no OH
proton signal was observed because of exchange. Mass
spectrum, m/z (Irel, %): 330 (6) [M]+, 139 (17), 119
(31), 91 (100), 65 (63). Found, %: C 68.84; H 3.00;
N 8.43. C19H10N2O4. Calculated, %: C 69.09; H 3.05;
N 8.48. M 330.30.
1
(C=O), 1596 (C=C), 1296 (C–O–C). H NMR spec-
trum, δ, ppm: 7.61 t (2H, o-H, J = 7.8 Hz), 7.79 t (1H,
p-H, J = 7.5 Hz), 7.61 d (2H, m-H, J = 7.8 Hz), 8.48 s
(1H, 7-H), 8.94 s (1H, 4-H), 9.74 s (1H, CHO).
Mass spectrum, m/z (Irel, %): 300 (100) [M]+, 271 (22)
[M – COH]+, 244 (51), 215 (27), 195 (21), 139 (24),
105 (30), 77 (85). Found, %: C 71.73; H 2.65; N 9.29.
C18N8N2O3. Calculated, %: C 72.00; H 2.69; N 9.33.
M 300.28.
Compounds 5c–5f (general procedure). Com-
pound 2c–2f, 1 mmol, was added to a solution of
0.46 g (3 mmol) of POCl3 in 3 mL of DMF, and the
mixture was stirred for 3 h at 80–90°C, cooled, and
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CHIRKOVA, FILIMONOV
1302
poured into a cold 5% solution of NaHCO3. The pre-
cipitate was filtered off, thoroughly washed with water,
and dried in air.
5′-H, J = 4.9 Hz), 8.31 s (1H, 7-H), 8.58 s (1H, 4-H),
8.75 br.s (1H, CHO). Found, %: C 62.75; H 3.47;
N 11.15. C20H13N3O3S. Calculated, %: C 63.99;
H 3.49; N 11.19.
3-Benzoyl-2-[(1E)-1-(dimethylamino)-3-oxoprop-
1-en-2-yl]-1-benzofuran-5,6-dicarbonitrile (5c).
Yield 0.31 g (84%), mp 238–240°C (decomp.). IR
spectrum, ν, cm–1: 2224 (CN), 1646 (C=O), 1621
9-Chloro-6-formyldibenzo[b,d]furan-2,3-dicar-
bonitrile (6). Compound 2a, 0.28 g (1 mmol), was
added to a solution of 0.46 g (3 mmol) of POCl3 in
3 mL of DMF, and the mixture was stirred for 3 h at
room temperature and poured into a cold 5% solution
of NaHCO3. The precipitate was filtered off,
thoroughly washed with water, and dried in air. Yield
0.24 g (85%), mp 287–289°C (decomp.). IR spectrum,
ν, cm–1: 2232 (CN), 1702 (C=O), 1598 (C=Carom).
1H NMR spectrum, δ, ppm: 7.73 d (1H, 8-H, J =
7.9 Hz), 8.14 d (1H, 7-H, J = 7.9 Hz), 8.75 s (1H,
1
(C=C), 1269 (C–O–C). H NMR spectrum, δ, ppm:
2.79 br.s [6H, N(CH3)2], 7.57 d (2H, o-H, J = 7.6 Hz),
7.70 t (1H, p-H, J = 7.6 Hz), 7.73 d (2H, m-H, J =
7.6 Hz), 8.00 s (2H, 7-H, NCH=), 8.33 s (1H, 4-H),
8.75 s (1H, CHO). Found, %: C 71.36; H 4.07;
N 11.31. C22H15N3O3. Calculated, %: C 71.54; H 4.09;
N 11.38.
2-[(E)-1-(Dimethylamino)-3-oxoprop-1-en-2-yl]-
3-(4-methylbenzoyl)benzofuran-5,6-dicarbonitrile
(5d). Yield 0.35 g (90%), mp 243–245°C (decomp.).
IR spectrum, ν, cm–1: 2226 (CN), 1667 (C=O), 1619
13
4-H), 8.84 s (1H, 1-H), 10.29 s (1H, CHO). C NMR
spectrum, δC, ppm: 110.24 (C2), 113.81 (C3), 115.57
(2-CN), 115.62 (3-CN), 118.67 (C4), 120.22 (C6),
120.54 (C9a), 125.23 (C8) 125.53 (C9b), 128.04 (C1),
132.97 (C7), 134.03 (C9), 155.46 (C5a), 156.10 (C4a),
187.52 (CHO). Mass spectrum, m/z (Irel, %): 280 (74)
[M]+, 279 (100), 252 (7) [M – 27]+, 225 (31), 223 (92),
189 (44), 140 (31), 111 (38), 86 (39). Found, %:
C 64.01; H 1.76; N 9.97. C15H5ClN2O2. Calculated, %:
C 64.19; H 1.80; N 9.98. M 280.67.
1
(C=C), 1258 (C–O–C). H NMR spectrum, δ, ppm:
2.38 s (3H, CH3), 7.26 d (2H, m-H, J = 7.93 Hz),
7.59 s (1H, NCH=), 7.60 d (2H, o-H, J = 7.93 Hz),
8.32 s (1H, 7-H), 8.61 s (1H, 4-H), 8.63 s (1H, CHO).
Mass spectrum, m/z (Irel, %): 383 (3) [M]+, 355 (5)
[M – 28]+, 119 (80), 91 (100). Found, %: C 71.87;
H 4.43; N 10.94. C23H17N3O3. Calculated, %: C 72.05;
H 4.47; N 10.96. M 383.41.
Compounds 6 and 7. Compound 2a, 0.28 g
(1 mmol), or 1a, 0.22 g (1 mmol), was added to a solu-
tion of 0.46 g (3 mmol) of POCl3 in 3 mL of DMF. The
mixture was stirred for 3 h at 40–90°C, cooled, and
poured into a cold 5% solution of NaHCO3. The pre-
cipitate was filtered off and recrystallized 3–4 times
from dioxane to accumulate compound 7, and the
product was dried in air.
2-[(E)-1-(Dimethylamino)-3-oxoprop-1-en-2-yl]-
3-(4-methoxybenzoyl)benzofuran-5,6-dicarbonitrile
(5e). Yield 0.37 g (93%), mp 254–256°C (decomp.).
IR spectrum, ν, cm–1: 2227 (CN), 1664 (C=O), 1618
1
(C=C), 1256 (C–O–C). H NMR spectrum, δ, ppm:
2.94 s and 3.29 s (3H each, NCH3), 3.82 s (3H, OCH3),
6.96 d (2H, m-H, J = 8.80 Hz), 7.58 s (1H, NCH=),
7.66 d (2H, o-H, J = 8.80 Hz), 8.27 s (1H, 7-H), 8.58 s
(1H, 4-H), 8.65 br.s (1H, CHO). 13C NMR spectrum,
δC, ppm: 40.12 and 46.88 (NMe), 55.49 (OMe), 100.73
(CCHO'), 109.09 (C5), 109.58 (C6), 113.31 (Cm) 116.33
(CN), 116.41 (CN), 117.34 (C3), 117.81 (C4), 126.94
(C7), 130.40 (Ci), 131.12 (Co), 132.40 (C3a), 153.35
(C7a), 158.47 (C2), 161.31 (NCH=), 162.86 (Cp),
184.50 (CHO), 188.01 (C=O). Mass spectrum:
m/z 422.1111. Calculated: [M + Na]+ 422.1117.
9-Chloro-6,8-diformyldibenzo[b,d]furan-2,3-di-
carbonitrile (7). Yield 0.05 g (16%), mp >300°C
(decomp.). IR spectrum, ν, cm–1: 2234 (CN), 1701
1
(C=O), 1596 (C=Carom). H NMR spectrum, δ, ppm:
8.68 s (1H, 7-H), 8.96 s (1H, 4-H), 9.22 s (1H, 1-H),
10.40 s (1H, 6-CHO), 10.49 s (1H, 8-CHO). Mass
spectrum, m/z (Irel, %): 308 (100) [M]+, 281 (41), 252
(17), 223 (92), 189 (39), 140 (29). Found, %: C 61.97;
H 1.59; N 9.05. C16H5ClN2O3. Calculated, %: C 62.26;
H 1.63; N 9.08. M 307.99.
2-[(E)-1-(Dimethylamino)-3-oxoprop-1-en-2-yl]-
3-(thiophen-2-ylcarbonyl)benzofuran-5,6-dicarbo-
nitrile (5f). Yield 0.29 g (76%), mp 216–218°C
(decomp.). IR spectrum, ν, cm–1: 2231 (CN), 1659
9-Chloro-6-(hydrazinylidenemethyl)dibenzo-
[b,d]furan-2,3-dicarbonitrile (8). Hydrazine hydrate,
0.10 mL (2 mmol), was added to a solution of 0.28 g
(1 mmol) of compound 6 in 3 mL of ethanol, and the
mixture was heated for 2 h under reflux. The mixture
was cooled, and the precipitate was filtered off,
washed with ethanol, and dried in air. Yield 0.24 g
(70%), mp >400°C. IR spectrum, ν, cm–1: 3297 (NH),
1
(C=O), 1618 (C=C), 1265 (C–O–C). H NMR spec-
trum, δ, ppm: 3.00 s and 3.35 s (3H each, NMe),
7.14 d.d (1H, 4′-H, J = 4.9, 3.9 Hz), 7.58 br.d (1H,
3′-H, J = 3.9 Hz), 7.72 s (1H, NCH=), 7.99 d (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 9 2016

SYNTHESIS OF FORMYL AND CARBOXY DERIVATIVES
1303
1
10. Schevenels, F. and Markó, I.E., Org. Lett., 2012,
vol. 14, p. 1298.
11. Schevenels, F., Tinant, B., Declercq, J.-P., and
2235 (CN), 1587 (C=Carom). H NMR spectrum, δ,
ppm: 7.46 s (2H, NH2), 7.51 d (1H, 8-H, J = 8.3 Hz),
7.83 d (1H, 7-H, J = 8.3 Hz), 8.04 s (1H, 4-H), 8.71 s
(1H, 1-H), 8.89 s (1H, NH). Found, %: C 60.98;
H 2.35; N 18.98. C15H7ClN4O. Calculated, %: C 61.14;
H 2.39; N 19.01.
Istvan, E.M., Chem. Eur. J., 2013, vol. 19, p. 4335.
12. Jackson, Y.A., Williams, M.F., Williams, L.A.D.,
Morgan, K., and Redway, F.A., Pestic. Sci., 1998,
vol. 53, p. 241.
9-Chloro-6-(hydroxymethyl)dibenzo[b,d]furan-
2,3-dicarbonitrile (9). Compound 6, 0.28 g (1 mmol),
was dissolved in 3 mL of ethanol, 0.11 g (3 mmol) of
NaBH4 was added, and the mixture was stirred for
1.5 h at 40°C. The mixture was cooled, and the precip-
itate was filtered off, washed with ethanol, and dried in
air. Yield 0.18 g (63%), mp >400°C. H NMR spec-
trum, δ, ppm: 4.89 s (2H, CH2), 5.66 br.s (1H, OH),
7.61 d (1H, 8-H, J = 7.9 Hz), 7.77 d (1H, 7-H, J =
13. Deprets, S. and Kirsch, G., Heterocycl. Commun., 2001,
vol. 7, p. 421.
14. Yuan Chen, Shaopeng Chen, Xin Lu, Hao Cheng,
Yingyong Oua, Huimin Cheng, and Guo-Chun Zhou,
Bioorg. Med. Chem. Lett., 2009, vol. 19, p. 1851.
15. Filimonov, S.I., Chirkova, Zh.V., Abramov, I.G., Shash-
kov, A.S., Firgang, S.I., and Stashina, G.A., Mendeleev
Commun., 2009, vol. 19, p. 332.
16. Chirkova, Zh.V., Filimonov, S.I., Danilova, A.S., and
Abramov, I.G., Izv. Vyssh. Uchebn. Zaved., Ser. Khim.
Khim. Tekhnol., 2011, vol. 54, no. 5, p. 20.
17. Vetelino, M.G. and Jotham, W.C., Tetrahedron Lett.,
1994, vol. 35, no. 2, p. 219.
18. Jong Keun Son, Jae Keun Son, and Yurngdong Jahng,
Heterocycles, 2002, vol. 57, no. 6, p. 1109.
19. Marson, Ch.M., Tetrahedron, 1992, vol. 48, p. 3659.
20. Gupton, J.T., Telang, N., Gazzo, D.F., Barelli, P.J.,
Lescalleet, K.E., Fagan, J.W., Mills, B.J., Finzel, K.L.,
Kanters, R.P.F., Crocker, K.R., Dudek, S.T.,
Lariviere, C.M., Smith, S.Q., and Keertikar, K.M.,
Tetrahedron, 2013, vol. 69, p. 5829.
1
13
7.9 Hz), 8.79 s (1H, 4-H), 8.98 s (1H, 1-H). C NMR
spectrum, δC, ppm: 56.97, 109.60, 113.04, 115.92,
116.01, 118.41, 124.91, 126.22, 126.25, 126.59,
127.90, 129.70, 154.62, 155.77, 166.39. Mass spec-
trum, m/z (Irel, %): 282 (21) [M]+, 281 (36) [M]+, 280
(74) [M]+, 279 (100) [M – H]+, 225 (31), 233 (93), 189
(45), 188 (39), 140 (31), 135 (24), 111 (39), 86 (38).
Found, %: C 63.61; H 2.48; N 9.87. C15H7ClN2O2.
Calculated, %: C 63.73; H 2.50; N 9.91. M 282.69.
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