Synthesis of Functionally Substituted Cyano Carbonyl Compounds

Article abstract of DOI:10.1134/S1070363217120234

Functionally substituted cyano carbonyl compounds have been synthesized by reactions of 1-chloro-oxiranecarbaldehyde acetals and α-chlorobenzyl diethoxymethyl ketones with potassium cyanide in DMF.

Full text of DOI:10.1134/S1070363217120234

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 12, pp. 2887–2890. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © M.F. Pistsov, O.M. Lavrova, A.M. Saifutdinov, R.N. Burangulova, L.M. Kustov, F.I. Guseinov, R.Z. Musin, 2017, published in
Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 12, pp. 2076–2079.
LETTERS
TO THE EDITOR
Dedicated to B.I. Buzykin on the 80th Anniversary of His Birth
Synthesis of Functionally Substituted
Cyano Carbonyl Compounds
a,b
a
a,b
a
M. F. Pistsov *, O. M. Lavrova , A. M. Saifutdinov , R. N. Burangulova ,
c
a,c
a,d
L. M. Kustov , F. I. Guseinov , and R. Z. Musin
a
Kazan National Research Technological University, ul. K. Marksa 68, Kazan, 420015 Tatarstan, Russia
e-mail: mihail.p.f@mail.ru
Immanuel Kant Baltic Federal University, ul. A. Nevskogo 14, Kaliningrad, 236016 Russia
*
b
c
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991 Russia
Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences,
d
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
Received July 31, 2017
Abstract—Functionally substituted cyano carbonyl compounds have been synthesized by reactions of 1-chloro-
oxiranecarbaldehyde acetals and α-chlorobenzyl diethoxymethyl ketones with potassium cyanide in DMF.
Keywords: chlorooxiranes, chloro ketones, potassium salts, potassium cyanide, cyanooxiranes
DOI: 10.1134/S1070363217120234
Chlorooxiranes containinf an acetal moiety are
promising starting compounds for the synthesis of
various heterocyclic systems, in particular heterocyclic
aldehydes and their derivatives. Our previous studies
have shown that chlorooxiranes 1 and isomeric chloro
ketones 2 react with O-, S-, P-, and N-mono- and
polynucleophiles to give various heterocycles via
formation of a new C–C bond and redox processes
leading to α-hydroxy acids [1–10].
pathway is nucleophilic substitution of halogen by cyano
group [11–16].
In order to extent the synthetic potential of
chlorooxiranes, we studied reactions of electrophiles 1
and 2 with potassium cyanide. The reactions were
carried out in DMF at room temperature (5–6 h), and
the products were potassium salts 4 (5) resulting from
opening of the oxirane ring (Scheme 1). We failed to
isolate the primary products, α-cyano ketones 3, since
they, being strong CH acids, reacted with the second
KCN molecule to form the corresponding potassium
salts capable of existing as both keto (4) and enolate
isomers (5).
It is known that reactions of halocarbonyl compounds
with cyanide ion take two main pathways. One pathway
involves attack of cyanide ion on the carbonyl carbon
atom with formation of cyanooxiranes or Favorskii
rearrangement leads to cyanocyclopropanols. The other
Scheme 1.
N
C
N
C
N
C
H
O
KCN, DMF
_KCl
KCN
CH(OEt)2
CH(OEt)2
CH(OEt)2
CH(OEt)2
R
_HCN
R
R
R
K
Cl
O
O
OK
а_1c
_
_
1
3
4а 4c
5а 5c
R = Ph (a), p-Cl-Ph (b), Me (c).
2
887

2
888
PISTSOV et al.
Scheme 2.
N
C
N
Cl
Cl
C
KCN, DMF
CH(OEt)2
CH(OEt)2
R
R
R
_Cl−
CH(OEt)
2
O
_
H
O
O
2
а, 2b
6а, 6b
R = Ph (a), p-Cl-Ph (b).
1
13
The product structure was proved by H and
C
α-Chloro ketones 2 reacted with potassium cyanide
in DMF at room temperature to give cyanooxiranes 6
in high yield (Scheme 2). The H NMR spectra of
1
NMR and MALDI mass spectra. The H NMR spectra
of 5 showed that both aromatic and acetal moieties
were conserved in their molecules. Signals in the
region δ ~6.9–8.1 ppm were assigned to aromatic protons,
and the acetal proton signal was a singlet at δ 5.4 ppm.
1
compounds 6 contained signals of the CH proton in the
oxirane ring (δ 4.49–4.51 ppm), acetal proton (δ 4.84–
4.86 ppm), and protons of the aromatic ring (δ 7.52–
1
3
1
3
7.78 ppm). In the C NMR spectrum of 6, the cyano
The enolate structure of 5 followed from the
NMR data. The α-carbon nucleus in enols resonates at
δ 140–160 ppm, and the β-carbon nucleus, at δ ~80–
C
carbon atom resonated at δ 115 ppm, and no carbonyl
C
carbon signal was observed.
C
C
1
00 ppm [17, 18]. The chemical shift of the double-
Potassium 1-cyano-3,3-diethoxy-1-phenylprop-1-
en-2-olate (5a). Chlorooxirane 1a, 1 g (3.90 mmol),
was added with stirring to a suspension of 0.506 g
(7.80 mmol) of potassium cyanide in 10 mL of DMF.
The mixture was stirred for 5 h at room temperature
and was then heated for 1 h at 80°C. The solvent was
removed under reduced pressure, the residue was
treated with 10 mL of ethanol, the precipitate was
filtered off, and the filtrate was evaporated. The white
crystalline solid was filtered off, washed with diethyl
ether (2–10 mL), and dried under reduced pressure.
Yield 0.62 g (65%), mp 150–153°C. IR spectrum, ν,
bonded carbon atom linked to the cyano group in
acrylonitriles is about 140 ppm, and the signal of the
other double-bonded carbon atom appears at δ 115
ppm or more upfield [19, 20]. Taking into account that
the β-carbon atom of the enol fragment of 5 is directly
linked to the cyano group, the chemical shifts of the
double-bonded carbon atoms are well consistent with
published data. Therefore, the signal at δ 72–73 ppm
can be assigned with a high degree of certainty to the
β-carbon atom, and the signal at δ ~179–180 ppm, to
the α-carbon atom. The signal at δ 120–123 ppm
C
C
C
C
–
1
belongs to the cyano group, since the range of
chemical shifts of the cyano carbon atoms in
acrylonitriles [19, 20] and some enol derivatives [17]
cm : 1055 s (C–O–C), 1537 s (C=Carom), 2170 s
1
(C≡N). H NMR spectrum (CDCl ), δ, ppm: 1.21 t
3
(6H, OCH CH , J = 6.6 Hz), 3.59–3.81 m (4H,
2
3
is δ ~115–120 ppm. Carbon atoms of the aromatic
OCH CH ), 5.50 s [1H, CH(OEt) ], 6.80 t (1H, p-H,
C
2 3 2
3
3
ring gave signals at δ ~140 and 127–123 ppm [17,
JHH = 7.2 Hz), 7.11 t (2H, m-H, J = 7.2 Hz), 8.11 d
HH
C
3
13
1
8]. The signals at δ ~15 and ~62 ppm belong to the
(2H, o-H, J = 7.6 Hz). C NMR spectrum (DMSO-
C
HH
methyl and methylene groups, respectively, and the
d ), δ , ppm: 15.71 (OCH CH ), 62.11 (OCH CH ),
6
C
2
3
2
3
acetal carbon atom has a chemical shift of δ ~100
ppm.
73.19 (NCC=C), 100.61 [CH(OEt) ], 121.08 (C≡N),
C
2
p
o
m
i
123.64 (C ), 127.65 (C ), 127.72 (C ), 140.13 (C ),
79.34 (C=COK). Mass spectrum (MALDI), m/z (I ,
1
rel
The mass spectrum of 5a showed a strong peak of
+
+
+
%): 286 (100) [M + H] , 324 (30) [M + K] . Found, %:
the protonated molecular ion [M + H] with m/z 286.
C 58.83; H 5.56; N 4.82. C H KNO . Calculated, %:
1
4
16
3
The ion with m/z 324 is heavier by 38 a.m.u., which
C 58.92; H 5.65; N 4.91.
corresponds to addition of potassium ion to the initial
+
molecule to give [M + K] . A different fragmentation
Potassium 1-(4-chlorophenyl)-1-cyano-3,3-dieth-
oxyprop-1-en-2-olate (5b) was synthesized in a
similar way from 1 g (3.436 mmol) of chlorooxirane
pattern was observed for compound 5b. In this case,
the most intense and informative were peaks with m/z
3
18 and 284. The first of these corresponds to
1b and 0.446 g (6.872 mmol) of KCN. Yield 0.7 g
+
1
elimination of hydrogen ([M – H] ), and the second, to
loss of chlorine from the molecular ion ([M – Cl] ).
(64%), mp 210–213°C. H NMR spectrum (CDCl ), δ,
3
+
ppm: 1.22 t (6H, OCH CH , J = 7.2 Hz), 3.19–3.58 m
2 3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 12 2017

SYNTHESIS OF FUNCTIONALLY SUBSTITUTED CYANO CARBONYL COMPOUNDS
4H, OCH CH ), 5.42 s [1H, CH(OEt) ], 7.09 (2H, m-
2889
(
59.80; H 5.83; Cl 12.62; N 5.08. C H ClNO .
14 16 3
2
3
2
3
3
13
H, J = 8.4 Hz), 8.11 d (2H, o-H, J = 8.4 Hz). C
Calculated, %: C 59.68; H 5.72; Cl 12.58; N 4.97.
HH
HH
NMR spectrum (DMSO-d6), δ , ppm: 15.79
C
The IR spectra were recorded in the range from 400
(
1
1
OCH CH ), 61.78 (OCH CH ), 72.77 (NCC=C),
–1
2
3
2
3
to 4000 cm on a Bruker Vektor 22 spectrometer with
p
00.35 [CH(OEt) ], 123.88 (C≡N), 124.56 (C ),
1
2
Fourier transform. The H NMR spectra were recorded
o
m
i
27.44 (C ), 127.48 (C ), 139.66 (C ), 180.08
13
on a Tesla BW 567 spectrometer (100 MHz). The C
(
(
5
C=COK). Mass spectrum (MALDI), m/z (I , %): 318
rel
NMR spectra were measured on a Bruker AM-300
instrument (300 MHz). The mass spectra (MALDI)
were obtained on a Bruker Ultraflex III instrument
+
+
100) [M – H] , 284 (45) [M – Cl] . Found, %: C
2.67; H 4.81; Cl 11.14; N 4.51. C H ClKNO .
1
4
15
3
Calculated, %: C 52.58; H 4.73; Cl 11.09; N 4.38.
(
Germany) equipped with a solid state laser and time-
of-flight mass analyzer. The purity of the isolated
compounds was checked by TLC on ALUGRAM SIL
G/UV ; spots were visualized by treatment with
Potassium 3-cyano-1,1,-diethoxybut-2-en-2-olate
5c) was synthesized in a similar way from 1 g
5.137 mmol) of chlorooxirane 1c and 0.667 g
(
(
(
2
54
iodine vapor and under UV light (λ 254, 365 nm).
10.274 mmol) of KCN. Yield 0.73 g (64%), mp 173–
1
1
75°C. H NMR spectrum (DMSO-d ), δ, ppm: 1.10 t
6
ACKNOWLEDGMENTS
(
6H, OCH CH , J = 7.0 Hz), 1.47 s (3H, CH ), 3.34–
2 3 3
1
3
3
.67 m (4H, OCH CH ), 4.99 s [1H, CH(OEt) ].
C
This study was performed under financial support
by the Russian Science Foundation (project no. 14-50-
00126) and also by of the 5-100 project for increasing
the rating of leading Russian universities among
world’s scientific educational centers.
2
3
2
NMR spectrum (DMSO-d ), δ , ppm: 15.79 (OCH CH ),
6
C
2
3
2
1
6.25 (CH C=C), 61.78 (OCH CH ), 72.77 (NCC=C),
3 2 3
00.35 [CH(OEt) ], 123.34 (C≡N), 180.07 (C=COK).
2
Found, %: C 48.52; H 6.43; N 6.38. C H KNO .
9
14
3
Calculated, %: C 48.41; H 6.32; N 6.27.
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(
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m
i
1
6
6
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(
40 mmol) of KCN. The product was isolated by
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9
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(
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3
1
4
.48 m (6H, OCH CH ), 3.76–3.91 m (4H, OCH CH ),
2 3 2 3
.51 s (1H, 3-H), 4.86 s [1H, CH(OEt) ], 7.78 s (4H,
2
13
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4
6
C
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2 3 2 3
3
o
(
C ), 100.02 [CH(OEt) ], 115.14 (C≡N), 126.21 (C ),
2
p
m
i
1
28.26 (C ), 129.16 (C ), 132.76 (C ). Found, %: C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 12 2017

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