Synthesis of functionalized alkyl-substituted cyclohexanones, pyridines, and 2,3,5,6,7,8-hexahydroisoquinolines by condensation of aliphatic aldehydes with CH acids

Article abstract of DOI:10.1134/S1070428014120136

Functionalized alkyl-substituted cyclohexanones, pyridines, and 2,3,5,6,7,8-hexahydroisoquinolines were synthesized by condensation of aliphatic aldehydes with CH acids.

Full text of DOI:10.1134/S1070428014120136

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 12, pp. 1787–1796. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © V.D. Dyachenko, E.N. Karpov, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 12, pp. 1806–1815.
Synthesis of Functionalized Alkyl-Substituted Cyclohexanones,
Pyridines, and 2,3,5,6,7,8-Hexahydroisoquinolines
by Condensation of Aliphatic Aldehydes with CH Acids
V. D. Dyachenko and E. N. Karpov
Taras Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine
e-mail: dyachvd@mail.ru
Received March 21, 2014
Abstract—Functionalized alkyl-substituted cyclohexanones, pyridines, and 2,3,5,6,7,8-hexahydroisoquinolines
were synthesized by condensation of aliphatic aldehydes with CH acids.
DOI: 10.1134/S1070428014120136
Aliphatic aldehydes are widely used in organic syn-
thesis due to their accessibility and high reactivity as
compared to aromatic aldehydes [1]. However, as we
reported previously [2], enhanced reactivity of aliphat-
ic aldehydes is responsible for substantially reduced
selectivity of their reactions, yields of target products,
and predictability of the product structure.
intermediate D which undergoes chemoselective intra-
molecular cyclization to final products V.
The condensation of isobutyraldehyde (If) with
cyanothioacetamide (IV) and 3-methyl-1H-pyrazol-
5(4H)-one (VI) in ethanol at 20°C in the presence of
morpholine gave stable Michael adduct VII, presum-
ably through intermediate E (Scheme 2). No subse-
quent intramolecular cyclization of VII occurred
because of its poor solubility and reduced reactivity of
the lactam carbonyl group in the pyrazole ring.
In continuation of our studies on the chemistry of
aliphatic aldehydes [3], the present work was aimed at
extending their synthetic potential for the preparation
of carbo- and heterocyclic compounds. The condensa-
tion of aldehydes Ia–If with 1,3-dicarbonyl com-
pounds IIa and IIb in ethanol at 0–5°C in the presence
of piperidine afforded exclusively substituted cyclo-
hexanones IIIa–IIIh, regardless of the reactant ratio.
Taking this fact into account, the condensation was
carried out with 2 equiv of CH acid II, which resulted
in sharp increase of the yield. The primary Knoeve-
nagel condensation product, intermediate A, could not
be isolated, obviously because of its rapid transforma-
tion into adduct B via Michael reaction. It should be
noted that aromatic aldehydes behave similarly in the
condensation with CH acids IIa and IIb [4]. The sub-
sequent intramolecular Knoevenagel condensation
through carbanion C yields 2-alkylcyclohexanones
IIIa–IIIh (Scheme 1). Like 3-aryl(hetaryl)-substituted
analogs [5], compounds III readily reacted with cyano-
thioacetamide (IV) in ethanol at 50°C in the presence
of morpholine to produce 3-thioxo-2,3,5,6,7,8-hexa-
hydroisoquinoline derivatives Va and Vb which may
be promising as antimicrobial agents [6]. The reaction
is likely to involve Knoevenagel condensation through
The structure of compounds IIIa–IIIh, Va, Vb, and
VII was determined on the basis of spectral data.
1
Cyclohexanones IIIa–IIIh displayed in the H NMR
spectra signals typical of alkyl groups (see Experimen-
tal) and those characteristic of protons in the cyclohex-
ane ring with appropriate couplings [7]. The mass
spectra of IIIa–IIIh contained [M + 1]+ ion peaks. The
1H NMR spectra of isoquinoline-3-thiones Va and Vb
resembled the spectra of their 8-aryl-(hetaryl)-substi-
tuted analogs, which were reported by us previously
[8]. In the IR spectra of Va and Vb we observed
absorption bands typical of stretching vibrations of
carbonyl, hydroxy, and amino groups and conjugated
cyano group (2218–2221 cm–1). Michael adduct VII
showed in the mass spectrum [M + 1]+ ion peak, which
is typical of basic compounds [9].
The reaction of aliphatic aldehydes Ia–Ie, Ig, and
Ih with cyanothioacetamide (IV) in ethanol at 20°C in
the presence of morpholine also involved initial forma-
tion of Knoevenagel condensation product F which
was not isolated but underwent further transformation
where it acted as Michael acceptor. The donor was
1787

DYACHENKO, KARPOV
1788
Scheme 1.
O
O
O
Me
O
O
Piperidine
EtOH
–H+
O
O
R
Me
Me
R
O
IIa, IIb
CH2
O
R
Me
Alk CHO +
R
Me
OH
O
Alk
Alk
O
Alk
R
R
O
O
Ia–If
IIa, IIb
A
B
C
R
Me
O
Me
Me
OH
Me
OH
NCCH2C(=S)NH2 (IV)
morpholine, EtOH
O
O
Me
CN
CN
S
R = Me
–H2O
Alk
O
Alk
Alk
S
··
R
IIIa–IIIh
Me
O
Me
N
H
NH2
D
Va, Vb
I, Alk = Me (a), Et (b), Pr (c), i-Bu (d), C6H13 (e), i-Pr (f); II, R = Me (a), EtO (b); III, R = Me, Alk = Me (a), Et (b), C6H13 (c),
i-Bu (d), i-Pr (e), Pr (f); R = EtO, Alk = i-Pr (g), Pr (h); V, Alk = Me (a), Et (b).
Scheme 2.
Me
O
N
NH
N
VI
NH
Me
O
NC
S
Morpholine
If
+ IV
NH2
S
i-Pr
i-Pr
NH2
NC
VII
E
another molecule of aliphatic aldehyde I due to acidic
properties of hydrogen in the α-position [1]. Intra-
molecular cyclization of the resulting Michael adduct
G gave substituted tetrahydropyridine-2-thione H, and
the latter was oxidized on exposure to air, as reported
previously for aryl(hetaryl)-substituted analogs [10].
The final products were morpholinium pyridine-
thiolates VIIIa–VIIIc (Scheme 3). When initial com-
pounds I and IV were taken in equimolar amounts, the
yield of VIII was low. The use of 2 equiv of aliphatic
aldehyde I considerably increased the yield, which
confirmed the proposed scheme for the formation of
salts VIII.
thiol K which exists as thione tautomer IX both in
crystal and in DMSO solution.
The structure of compounds VIIIa–VIIIc and IX
was confirmed by spectral data and chemical trans-
formations. By alkylation of salts VIII with chloro-
acetanilides Xa and Xb we obtained the corresponding
sulfides XIa and XIb (Scheme 5); the formation of the
latter may be regarded as a qualitative test for thioxo
group in the series of pyridine-2-thiones [12]. Com-
pounds XIa and XIb can also be obtained directly from
aliphatic aldehyde, cyanothioacetamide, and chloro-
acetanilide; sulfide XIb was synthesized in this way.
Alkylation of pyridinethione IX with chloroacet-
amide XII in DMF in the presence of alkali was also
regioselective, and the product was sulfide XIII
(Scheme 6). The latter was converted into substituted
2-aminothieno[2,3-b]pyridine XIV by the action of
alkali. This transformation confirmed vicinal arrange-
ment of the cyano and thioxo groups in molecule IX
[13]. The subsequent condensation of XIV with cyclo-
hexanone in boiling glacial acetic acid afforded substi-
tuted 1′H-spiro[cyclohexane-1,2′-pyrido[3′,2′:4,5]-
We failed to isolate the corresponding salt in the
reaction of acetaldehyde (Ia) with cyanothioacetamide
(IV). However, treatment of the reaction mixture with
aqueous HCl gave 4-methyl-2-thioxo-1,2-dihydropyri-
dine-3-carbonitrile (IX) (Scheme 4). Compound IX
was synthesized by us previously by condensation of
crotonaldehyde with cyanothioacetamide in boiling
ethanol in the presence of sodium ethoxide [11]. The
reaction is likely to involve formation of pyridine-2-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

SYNTHESIS OF FUNCTIONALIZED ALKYL-SUBSTITUTED CYCLOHEXANONES
1789
Scheme 3.
Alk
NC
S
R
CN
S
Morpholine
Ib–Id
Ib–Id
+
IV
Alk
NH2
··
O
NH2
F
G
Alk
Alk
Alk
R
CN
R
CN
R
CN
NH2
·
O
–2[H]
N
S
N
S
N
S–
H
J
VIIIa–VIIIc
VIII, Alk = Et, R = Me (a); Alk = Pr, R = Et (b); Alk = i-Bu, R = i-Pr (c).
Scheme 4.
Me
N
Me
Me
CN
S–
CN
SH
CN
S
H+
Morpholine
Ia
Ia
+
IV
F
G
H
J
N
N
H
K
IX
thieno[3,2-d]pyrimidine] XV which is a potential anti-
microbial agent [13]; its formation confirmed vicinal
position of the amino group with respect to the
carbamoyl group in structure XIV [13, 14].
Apart from the base peak with m/z 207 [M]+,
the mass spectrum of thienopyridine XIV contained
[M + 2]+ ion peak with m/z 209 (Irel 4%), which
indicated the presence of a sulfur atom in its molecule
[15]. In addition, the odd m/z value of the molecular
ion shows that molecule XIV contains an odd number
of nitrogen atoms, in keeping with the “nitrogen
rule” [16].
Unexpectedly, the condensation of aldehydes Ig
and Ih with an equimolar amount of cyanothioacet-
amide (IV) in ethanol at 20°C in the presence of mor-
pholine gave morpholinium 4-alkyl-6-amino-3,5-dicy-
anopyridine-2-thiolates XVIa and XVIb (Scheme 7).
Presumably, increased positive inductive effect of long
alkyl groups in aldehydes Ig and Ih reduces the CH
acidity of the α-methylene group. As a result, the reac-
tion follows an alternative path according to which
Michael addition of the second cyanothioacetamide
(IV) molecule to intermediate Knoevenagel condensa-
tion product F yields adduct L. The latter undergoes
chemoselective intramolecular cyclization, and subse-
quent dehydration and elimination of hydrogen sulfide
lead to morpholinium salt XVI. This scheme is sup-
ported by sharp increase of the yield of XVI in the
reaction with 2 equiv of cyanothioacetamide (IV). It
should be noted that aromatic aldehydes having no
CH-acidic groups reacted in a similar way with 2 equiv
of cyanothioacetamide (IV) in the presence of amines
at room temperature; the isolated products were am-
monium 6-amino-4-aryl-3,5-dicyanopyridine-2-
thiolates [17].
The structure of compounds XVIa and XVIb was
confirmed by spectral data, as well as by alkylation
with chloroacetamide (XII) and benzyl chloride
Scheme 5.
Pr
N
Et
CN
S
4-BrC6H4NHC(O)CH2Cl (Xb)
4-MeOC6H4NHC(O)CH2Cl (Xa)
2Ie
+
IV
VIIIb
H
N
C6H4X-4
O
XIa, XIb
X = MeO (a), Br (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

DYACHENKO, KARPOV
1790
Scheme 6.
Me
N
O
Me
Me
N
NH2
HN
CN
ClCH2C(O)NH2 (XII)
KOH
NH
O
KOH
AcOH
NH2
O
IX
NH2
S
S
S
N
O
XIII
XIV
XV
Scheme 7.
Alk
N
Alk
NC
CN
NH2
NC
CN
Morpholine
–H2O
IV
Ig, Ih
+
IV
F
–H2S, –2[H]
O
H2N
S
H2N
S–
··
S
NH2
L
XVIa, XVIb
Alk
N
NC
CN
XII, PhCH2Cl (XVII)
H2N
S
X
XVIIIa–XVIIIc
I, Alk = C7H15 (g), C9H19 (h); XVI, Alk = C7H15 (a), C9H19 (b); XVIII, Alk = C7H15, X = CONH2 (a), Ph (b);
Alk = C9H19, X = Ph (c).
(XVII) which afforded expected sulfides XVIIIa–
XVIIIc. The IR spectra of XVIIIa–XVIIIc contained
absorption bands due to stretching vibrations of con-
jugated cyano groups (2218–2224 cm–1) and amino
group (3115–3430 cm–1) and N–H bending vibrations
(1642–1652 cm–1). In the 1H NMR spectra of XVIIIa–
XVIIIc, the SCH2 signal was a singlet at δ 3.84–
4.44 ppm, which is consistent with published data for
structurally related compounds [17, 18].
propanoate (XIX) as CH acid (EtOH, EtONa, 20°C).
Presumably, intermediate Knoevenagel adduct M takes
up the second CH acid molecule XIX to give Michael
adduct N, and the latter undergoes chemoselective
intramolecular cyclization with elimination of ethanol
and hydrogen sulfide, yielding pyridine-2-thiolate O
(Scheme 8). It is known that addition of hydrogen
sulfide to a cyano group is reversible [19], and facile
elimination of H2S from CH acids containing a thio-
amide group was observed previously [20].
Functionally substituted pyridin-2(1H)-ones XXa
and XXb were obtained by condensation of aldehydes
Id and Ie with 2 equiv of ethyl 3-amino-3-thioxo-
However, we failed to isolate pure salt O because
of its high hydrophilicity. Treatment of the reaction
Scheme 8.
S
O
Alk
S
O
S
O
XIX
H2N
EtO
OEt
Id, Ie
+
H2N
OEt
H2N
Alk
OEt
S
··
XIX
Alk
O
NH2
M
N
O
Alk
O
Pr-i
O
BrCH2CH=CH2 (XXI)
KOH
H+
NC
O
NC
O
NC
O
OEt
S– Na+
OEt
OEt
–EtOH
–H2S
Alk = i-Pr
CH2
N
H
N
H
SH
N
H
S
O
XXa, XXb
XXII
XX, Alk = i-Bu (a), C6H13 (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

SYNTHESIS OF FUNCTIONALIZED ALKYL-SUBSTITUTED CYCLOHEXANONES
1791
mixture with hydrochloric acid led to the formation of
stable 6-sulfanylpyridin-2-ones XXa and XXb. Their
structure was confirmed by spectral data (see Experi-
mental). The alkylation of XXa with allyl bromide
(XXI) in DMF in the presence of alkali gave the corre-
sponding allyl sulfide XXII which showed the follow-
m/z 225 (Irel 100%) [M – l]+. Found, %: C 63.58;
H 7.93. C12H18O4. Calculated, %: C 63.70; H 8.02.
M 226.27.
2,4-Diacetyl-3-ethyl-5-hydroxy-5-methylcyclo-
hexan-1-one (IIIb). Yield 1.32 g (55%), light yellow
crystals, mp 108–110°C. IR spectrum, ν, cm–1: 3358
1
1
ing signals of the allyl fragment in the H NMR spec-
trum, δ, ppm: 3.64 d (2H, CH2, J = 6.4 Hz), 5.01 d
(OH); 1733, 1679 (C=O). H NMR spectrum, δ, ppm:
0.75 d (3H, Me, J = 6.8 Hz), 1.02–1.32 m (5H, CH2,
Me), 2.02–2.32 m (7H, Me, 6-H), 2.65–2.78 d (2H,
4-H, 6-H), 2.91–3.12 m (1H, 3-H), 3.59 d (1H, 2-H,
J = 11.5 Hz), 5.13 br.s (1H, OH). Mass spectrum:
m/z 239 (Irel 100%) [M – 1]+. Found, %: C 64.82;
H 8.29. C13H20O4. Calculated, %: C 64.98; H 8.39.
M 240.30.
(1H, CH2=, Jcis = 9.9 Hz), 5.19 d (1H, CH2=, Jmpans
=
16.9 Hz), 5.73–5.94 m (1H, CH=) [21].
EXPERIMENTAL
The IR spectra were measured in KBr on a Perkin
Elmer Spectrum One spectrometer. The 1H NMR spec-
tra were obtained on a Varian VXR-400 instrument at
399.97 MHz using DMSO-d6 as solvent and tetra-
methylsilane as internal reference. The mass spectra
(electron impact, 70 eV) were obtained on a Hewlett
Packard HP 5972 mass-selective detector coupled with
an HP 5890 gas chromatograph (HP-5MS column;
samples were injected as solutions in CH2Cl2) and on
a Kratos MS-890 mass spectrometer with direct
sample admission into the ion source (compounds VII,
XIV, XVIa, XVIb). The melting points were deter-
mined on a Kofler hot stage. The progress of reactions
and the purity of products were monitored by TLC on
Silufol UV-254 plates using acetone–hexane (3:5) as
eluent; spots were visualized under UV light and by
treatment with iodine vapor.
2,4-Diacetyl-3-hexyl-5-hydroxy-5-methylcyclo-
hexan-1-one (IIIc). Yield 1.8 g (61%), yellow crystals,
mp 77–79°C. IR spectrum, ν, cm–1: 3365 (OH); 1728,
1
1680 (C=O). H NMR spectrum, δ, ppm: 0.85 t (3H,
Me, J = 6.3 Hz), 1.05–1.32 m (13H, Me, CH2), 2.21 s
(3H, MeCO), 2.23 s (3H, MeCO), 2.27–2.33 m (2H,
4-H, 6-H), 2.93–3.14 m (2H, 3-H, 6-H), 3.55 d (1H,
2-H, J = 11.6 Hz), 5.01 br.s (1H, OH). Mass spectrum:
m/z 295 (Irel 100%) [M – 1]+. Found, %: C 68.77; H 9.47.
C17H28O4. Calculated, %: C 68.89; H 9.52. M 296.41.
2,4-Diacetyl-5-hydroxy-3-isobutyl-5-methylcyclo-
hexan-1-one (IIId). Yield 1.7 g (65%), yellow crys-
tals, mp 79–80°C. IR spectrum, ν, cm–1: 3388 (OH);
1
1722, 1679 (C=O). H NMR spectrum, δ, ppm: 0.76 d
(3H, Me, J = 6.3 Hz), 0.81 d (3H, Me, J = 6.3 Hz),
0.93–1.08 m (2H, CH2), 1.19 s (3H, Me), 1.41–1.52 m
(4H, Me, CHMe2), 2.18–2.29 m (5H, Me, 2-H, 6-H),
2.37–2.54 m (3H, 3-H, 4-H, 6-H), 6.27 br.s (1H, OH).
Mass spectrum: m/z 267 (Irel 100%) [M – 1]+. Found,
%: C 67.02; H 8.95. C15H24O4. Calculated, %: C 67.14;
H 9.01. M 268.35.
3-Alkyl-2,4-diacetyl(ethoxycarbonyl)-5-hydroxy-
5-methylcyclohexanones IIIa–IIIh (general proce-
dure). A solution of 1 mL (10 mmol) of piperidine in
10 mL of ethanol was added dropwise under stirring
over a period of 5 min to a mixture of aliphatic alde-
hyde Ia–If and 20 mmol of CH acid IIa or IIb,
maintaining the temperature at 0–5°C. The mixture
was kept for 48 h at 0°C and treated with diethyl ether
(4×10 mL). The combined extracts were dried over
anhydrous sodium sulfate and evaporated, and the
residue was kept for 24 h at 0°C. The finely crystalline
powder was recrystallized from 50% ethanol.
2,4-Diacetyl-5-hydroxy-3-isopropyl-5-methyl-
cyclohexan-1-one (IIIe). Yield 1.5 g (59%), yellow
crystals, mp 128–130°C. IR spectrum, ν, cm–1: 3362
1
(OH); 1736, 1702 (C=O). H NMR spectrum, δ, ppm:
0.81 d (6H, Me, J = 6.6 Hz), 1.12–1.23 m (4H, Me,
CHMe2), 1.42–1.48 m (1H, 3-H), 2.01–2.28 m (4H,
Me, 6-H), 2.31–2.46 m (4H, Me, 2-H), 2.58 d (1H,
6-H, J = 11.8 Hz), 2.67 d (1H, 4-H, J = 11.6 Hz),
6.19 br.s (1H, OH). Mass spectrum: m/z 253
(Irel 100%) [M – 1]+. Found, %: C 66.01; H 8.65.
C14H22O4. Calculated, %: C 66.12; H 8.72. M 254.33.
2,4-Diacetyl-5-hydroxy-3,5-dimethylcyclohexan-
1-one (IIIa). Yield 1.53 g (68%), colorless crystals,
mp 90–91°C. IR spectrum, ν, cm–1: 3362 (OH); 1735,
1
1683 (C=O). H NMR spectrum, δ, ppm: 0.75 d (3H,
Me, J = 6.3 Hz), 1.13 s (3H, Me), 2.12 s (3H, MeCO),
2
2.19 s (3H, MeCO), 2.24 d (1H, CH2, J = 13.7 Hz),
2,4-Diacetyl-5-hydroxy-5-methyl-3-propylcyclo-
hexan-1-one (IIIf). Yield 1.8 g (69%), yellow crystals,
mp 115–116°C. IR spectrum, ν, cm–1: 3381 (OH);
2
2.58 d (1H, CH, J = 11.9 Hz), 2.72 d (1H, CH2, J =
13.7 Hz), 2.81–2.92 m (1H, CHMe), 3.45 d (1H, CH,
J = 11.6 Hz), 5.09 br.s (1H, OH). Mass spectrum:
1
1722, 7696 (C=O). H NMR spectrum, δ, ppm: 0.77 t
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

DYACHENKO, KARPOV
1792
(3H, Me, J = 6.5 Hz), 1.06–1.23 m (7H, Me, CH2),
2.13 s (3H, MeCO), 2.20 s (3H, MeCO), 2.24 d (1H,
6-H, J = 13.8 Hz), 2.72 d (2H, 2-H, 6-H, J = 12.8 Hz),
2.92–3.03 m (1H, 3-H), 3.57 d (1H, 4-H, J = 11.6 Hz),
5.09 br.s (1H, OH). Mass spectrum: m/z 253
(Irel 100%) [M – 1]+. Found, %: C 65.99; H 8.64.
C14H22O4. Calculated, %: C 66.12; H 8.72. M 254.33.
%: C 61.95; H 6.11; N 9.50. CI5H18N2O2S. Calculated,
%: C 62.04; H 6.25; N 9.65. M 290.38.
7-Acetyl-8-ethyl-6-hydroxy-1,6-dimethyl-3-
thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbo-
nitrile (Vb) was synthesized in a similar way from
2.4 g (10 mmol) of compound IIIb. Yield 1.7 g (57%),
yellow–green crystals, mp 217–218°C (from EtOH).
IR spectrum, ν, cm–1: 3388 (OH), 3283 (NH), 2221
Diethyl 4-hydroxy-2-isopropyl-4-methyl-6-oxo-
cyclohexane-1,3-dicarboxylate (IIIg). Yield 1.8 t
(57%), colorless crystals, mp 118–120°C. IR spectrum,
ν, cm–1: 3466 (OH); 1745, 1700 (C=O). 1H NMR spec-
trum, δ, ppm: 0.75 d (3H, Me, J = 7.1 Hz), 0.92 d (3H,
Me, J = 7.1 Hz), 1.15 s (3H, Me), 1.16 t (3H, Me, J =
7.1 Hz), 1.22 t (3H, Me, J = 7.1 Hz), 1.62–1.73 m (1H,
1
(C≡N), 1699 (C=O), 1198 (C=S). H NMR spectrum,
δ, ppm: 0.75 t (3H, Me, J = 6.9 Hz), 1.32–1.58 m (5H,
Me, CH2), 2.19 s (3H, Me), 2.46 s (3H, Me), 2.75 d
2
(1H, 7-H, J = 3.6 Hz), 2.81 d (1H, 5-H, J = 16.3 Hz),
2.95 d (1H, 5-H, 2J = 16.3 Hz), 3.07–3.22 m (1H, 8-H),
4.78 br.s (1H, OH), 13.75 br.s (1H, NH). Mass spec-
trum: m/z 303 (Irel 100%) [M – 1]+. Found, %: C 63.00;
H 6.48; N 9.11. C16H20N2O2S. Calculated, %: C 63.13;
H 6.62; N 9.20. M 304.41.
2
CHMe2), 2.19 d (1H, 6-H, J = 14.3 Hz), 2.19–2.26 m
(1H, 2-H), 2.81 d (1H, 1-H, J = 6.8 Hz), 2.86 d (1H,
2
6-H, J = 14.3 Hz), 3.76 d (1H, 3-H, J = 12.7 Hz),
4.05–4.18 m (4H, CH2), 5.19 br.s (1H, OH). Mass
spectrum, m/z (Irel, %): 297 (10) [M – OH]+, 251 (100)
[M – EtOH – OH]+. Found, %: C 61.01; H 8.25.
C16H26O6. Calculated, %: C 61.13; H 8.34. M 314.38.
2-Cyano-4-methyl-3-(3-methyl-5-oxo-4,5-dihy-
dro-1H-pyrazol-4-yl)pentanethioamide (VII). To
a solution of 0.91 mL (10 mmol) of isobutyraldehyde
(If) in 20 mL of anhydrous ethanol we added at 20°C
under stirring in succession 1 g (10 mmol) of cyano-
thioacetamide (IV), one drop of morpholine, and
0.98 g (10 mmol) of pyrazolone VI, and the mixture
was left to stand for 3 days. The precipitate was
filtered off and washed with ethanol and hexane. Yield
1.7 g (69%), yellow powder, mp 222–224°C (from
EtOH). IR spectrum, ν, cm–1: 3540, 3450 (NH, NH2);
Diethyl 4-hydroxy-4-methyl-6-oxo-2-propyl-
cyclohexane-1,3-dicarboxylate (IIIh). Yield 2.1 g
(67%), colorless crystals, mp 99–100°C. IR spectrum,
ν, cm–1: 3412 (OH); 1739, 1711 (C=O). 1H NMR spec-
trum, δ, ppm: 0.85 t (3H, Me, J = 7.2 Hz), 1.10–1.33 m
(13H, Me, CH2), 2.21 d (1H, 5-H, 2J = 14.2 Hz), 2.68–
2.79 m (1H, 2-H), 2.81–2.93 m (2H, 1-H, 5-H), 3.58 d
(1H, 3-H, J = 2.4 Hz), 4.00–4.29 m (4H, CH2O),
5.22 br.s (1H, OH). Mass spectrum, m/z (Irel, %): 315
(8) [M + 1]+, 297 (50) [M – OH]+, 251 (100) [M –
EtOH – OH]+. Found, %: C 61.01; H 8.22. C16H26O6.
Calculated, %: C 61.13; H 8.34. M 314.38.
1
2254 (CN), 1670 (CONH), 1632 (δNH). H NMR
spectrum, δ, ppm: 0.81–1.12 m (9H, Me), 1.88–2.43 m
(1H, CHMe2), 3.44–3.81 m (2H, CH), 5.11 d (1H,
CHCN, J = 6.9 Hz), 10.11 br.s (1H, NH), 10.92 br.s
(2H, NH2). Mass spectrum, m/z (Irel, %): 253 (6)
[M + 1]+, 221 (9), 178 (14), 160 (10), 152 (19), 124
(9), 96 (27), 64 (82), 43 (100) [MeCHMe]+, 36 (94).
Found, %: C 52.21; H 6.22; N 22.04. C11H16N4OS.
Calculated, %: C 52.36; H 6.39; N 22.20. M 252.33.
7-Acetyl-6-hydroxy-1,6,8-trimethyl-3-thioxo-
2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile
(Va). A mixture of 2.3 g (10 mmol) of compound IIIa,
1 g (10 mmol) of cyanothioacetamide (IV), and
0.87 mL (10 mmol) of morpholine in 30 mL of anhy-
drous ethanol was stirred for 1 h at 50°C and was then
left to stand for 48 h at room temperature. The crystal-
line solid was filtered off and washed with ethanol and
hexane. Yield 1.8 g (63%), yellow crystals, mp 218–
220°C (from EtOH). IR spectrum, ν, cm–1: 3411 (OH),
3279 (NH), 2218 (C≡N), 1700 (C=O), 1201 (C=S).
1H NMR spectrum, δ, ppm: 1.05 d (3H, Me, J =
6.8 Hz), 1.35 s (3H, Me), 2.22 s (3H, Me), 2.46 s (3H,
Me), 2.61 d (1H, 7-H, J = 6.5 Hz), 2.79 d (1H, 5-H, J =
16.8 Hz), 2.97 d (1H, 5-H, 2J = 16.8 Hz), 3.21–3.28 m
(1H, 8-H), 4.83 br.s (1H, OH), 13.8 br.s (1H, NH).
Mass spectrum: m/z 289 (Irel 100%) [M – 1]+. Found,
Morpholinium 4-alkyl-5-R-3-cyanopyridine-2-
thiolates VIIIa–VIIIc (general procedure). A solution
of 10 mmol of the corresponding aldehyde I, 1 g
(10 mmol) of cyanothioacetamide (IV), and 0.87 mL
(10 mmol) of morpholine in 20 mL of ethanol was
stirred for 15 min at 20°C, an additional portion of the
aldehyde, 10 mmol, was added, and the mixture was
left to stand for 3 days. The precipitate was filtered off,
washed with ethanol and hexane, and recrystallized
from ethanol.
Morpholinium 3-cyano-4-ethyl-5-methylpyri-
dine-2-thiolate (VIIIa). Yield 1.6 g (59%), yellow
powder, mp 195–196°C. IR spectrum, ν, cm–1: 3436
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

SYNTHESIS OF FUNCTIONALIZED ALKYL-SUBSTITUTED CYCLOHEXANONES
1793
1
(NH2), 2215 (CN). H NMR spectrum, δ, ppm: 1.14 t
(3H, Me, J = 7.4 Hz), 2.12 s (3H, Me), 2.67 q (2H,
CH2, J = 7.4 Hz), 2.79 t (4H, CH2NCH2, J = 4.2 Hz),
3.57 t (4H, CH2OCH2, J = 4.2 Hz), 7.81 s (1H, 6-H);
N+H2 signal was not observed, presumably due to fast
H/D exchange. Mass spectrum, m/z (Irel, %): 177 (100)
[Manion]+, 88 (100) [Mcation]+. Found, %: C 58.75;
H 7.08; N 15.69. C13H19N3OS. Calculated, %: C 58.84;
H 7.22; N 15.83. M 265.37.
water, ethanol, and hexane. Yield 2.4 g (65%), yellow
powder, mp 128–130°C (from EtOH). IR spectrum, ν,
cm–1: 3395 (NH), 2222 (C≡N), 1674 (CONH).
1H NMR spectrum, δ, ppm: 1.00 t (3H, Me, J =
7.2 Hz), 1.16 t (3H, Me, J = 7.4 Hz), 1.48 m (2H,
CH2), 2.65 q (2H, CH2, J = 7.4 Hz), 2.75 t (2H, CH2,
J = 7.6 Hz), 3.72 s (3H, MeO), 4.18 s (2H, SCH2),
6.85 d and 7.49 d (2H each, Harom, J = 8.6 Hz), 8.47 s
(1H, 6-H), 10.23 br.s (1H, NH). Mass spectrum:
m/z 368 (Irel 100%) [M – 1]+. Found, %: C 64.87;
H 6.15; N 11.20. C20H23N3O2S. Calculated, %:
C 65.02; H 6.27; N 11.37. M 369.48.
Morpholinium 3-cyano-5-ethyl-4-propylpyri-
dine-2-thiolate (VIIIb). Yield 1.9 g (66%), yellow
powder, mp 116–118°C. IR spectrum, ν, cm–1: 3436
(NH2), 2219 (C≡N). 1H NMR spectrum, δ, ppm: 1.01 t
(3H, Me, J = 7.1 Hz), 1.11 t (3H, Me, J = 13 Hz),
1.48–1.69 m (2H, CH2), 2.52 t (2H, CH2, J = 7.6 Hz),
2.68 t (2H, CH2, J = 7.5 Hz), 2.79 t (4H, CH2NCH2,
J = 4.6 Hz), 3.55 t (4H, CH2OCH2, J = 4.6 Hz), 7.72 s
(1H, 6-H); N+H2 signal was not observed, presumably
due to fast H/D exchange. Mass spectrum, m/z (Irel, %):
205 (100) [Manion]+, 88 (100) [Mcation]+. Found, %:
C 61.33; H 7.78; N 14.28. C15H23N3OS. Calculated, %:
C 61.40; H 7.90; N 14.32. M 293.43.
N-(4-Bromophenyl)-2-(3-cyano-4-hexyl-5-pentyl-
pyridin-2-ylsulfanyl)acetamide (XIb) was synthe-
sized as described above for salts VIII from 2.8 mL
(20 mmol) of heptanal (Ie). 2-Chloro-N-(4-methoxy-
phenyl)acetamide (Xb), 2.5 g (10 mmol), was added to
the reaction mixture, and the mixture was stirred for
30 min and left to stand for 24 h. The precipitate was
filtered off and washed with water, ethanol, and hex-
ane. Yield 3.5 g (69%), yellow powder, mp 83–84°C
(from EtOH). IR spectrum, ν, cm–1: 3254 (NH), 2219
1
(C≡N), 1673 (CONH). H NMR spectrum, δ, ppm:
Morpholinium 3-cyano-4-isobutyl-5-isopropyl-
pyridine-2-thiolate (VIIIc). Yield 2.3 g (71%), yellow
powder, mp 134–136°C. IR spectrum, ν, cm–1: 3421
(NH2), 2213 (C≡N). 1H NMR spectrum, δ, ppm: 0.96 d
(6H, Me, J = 6.2 Hz), 1.16 d (6H, Me, J = 6.4 Hz),
1.78–1.95 m (1H, CH2CHMe2), 2.64 d (2H, CH2, J =
7.0 Hz), 2.81 t (4H, CH2NCH2, J = 4.1 Hz), 3.82–
3.05 m (1H, CHMe2), 3.58 t (4H, CH2OCH2, J =
4.1 Hz), 7.91 s (1H, 6-H); N+H2 signal was not ob-
served, presumably due to fast H/D exchange. Mass
spectrum: m/z 233 (Irel 100%) [Manion]+. Found, %:
C 63.39; H 8.30; N 12.88. C17H27N3OS. Calculated, %:
C 63.51; H 8.47; N 13.07.
0.87 t (6H, Me, J = 7.1 Hz), 1.14–1.69 m (14H, CH2),
2.51–2.55 m (2H, CH2), 2.75 t (2H, CH2, J = 7.2 Hz),
4.21 s (2H, SCH2), 7.48 d and 7.57 d (2H each, Harom
,
J = 8.6 Hz), 8.43 s (1H, 6-H), 10.55 br.s (1H, NH).
Mass spectrum: m/z 502 (Irel 100%) [M]+. Found, %:
C 59.68; H 6.31; N 8.20. C25H32BrN3OS. Calculated,
%: C 59.75; H 6.42; N 8.36. M 502.51.
2-(3-Cyano-4-methylpyridin-2-ylsulfanyl)acet-
amide (XIII). Pyridinethione IX, 1.5 g (10 mmol),
was dissolved in 15 mL of DMF, 5.6 mL (10 mmol) of
10% aqueous potassium hydroxide and 0.94 g
(10 mmol) of chloroacetamide (XII) were added in
succession under stirring at 20°C, and the mixture was
stirred for 4 h and diluted with an equal volume of
water. The precipitate was filtered off and washed with
water, ethanol, and hexane. Yield 1.6 g (75%), yellow
crystals, mp 208–209°C (from AcOH; sublimes at
175°C). IR spectrum, ν, cm–1: 3348, 3218 (NH2); 2216
4-Methyl-2-thioxo-1,2-dihydropyridine-3-carbo-
nitrile (IX) was synthesized as described above for
morpholinium salts VIII from 1.14 mL (20 mmol) of
acetaldehyde (Ia). The reaction mixture was diluted
with 10% aqueous HCl to pH 5 and left to stand for
2 days. The precipitate was filtered off and washed
with ethanol and hexane. Yield 1 g (64%), mp 245–
247°C; published data [12]: mp 248–250°C. Mass
spectrum: m/z 149 (Irel 100%) [M – 1]+.
1
(C≡N), 1670 (CONH). H NMR spectrum, δ, ppm:
2.42 s (3H, Me), 3.89 s (2H, CH2), 6.99 br.s (1H,
NH2), 7.13 d (1H, 5-H, J = 4.2 Hz), 7.37 br.s (1H,
NH2), 8.45 d (1H, 6-H, J = 4.2 Hz). Mass spectrum:
m/z 208 (Irel 100%) [M + 1]+. Found, %: C 52.02;
H 4.21; N 20.11. C9H9N3OS. Calculated, %: C 52.16;
H 4.38; N 20.27. M 207.25.
2-(3-Cyano-5-ethyl-4-propylpyridin-2-ylsul-
fanyl)-N-(4-methoxyphenyl)acetamide (XIa). A sus-
pension of 2.9 g (10 mmol) of salt VIIIb and 2 g
(10 mmol) of compound Xa in 25 mL of ethanol was
stirred for 3 h at 20°C and was then left to stand for
24 h. The precipitate was filtered off and washed with
3-Amino-4-methylthieno[2,3-b]pyridine-2-car-
boxamide (XIV). Sulfide XIII, 2.1 g (10 mmol), was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

DYACHENKO, KARPOV
1794
dissolved in 20 mL of DMF, 5.6 mL (10 mmol) of
10% aqueous potassium hydroxide was added under
stirring at 20°C, and the mixture was stirred for 5 h
and diluted with an equal volume of water. The precip-
itate was filtered off and washed with water, ethanol,
and hexane. Yield 1.6 g (76%), light yellow crystals,
mp 225–226°C (from BuOH; sublimes at 200°C). IR
spectrum, ν, cm–1: 3345, 3296, 3200 (NH2); 1675
H 7.42; N 19.20. C18H27N5OS. Calculated, %: C 59.80;
H 7.53; N 19.37. M 361.51.
Morpholinium 6-amino-3,5-dicyano-4-nonylpyr-
idine-2-thiolate (XVIb) was synthesized as described
above for salts VIII from 1.9 mL (10 mmol) of decanal
(Ih) and 2 g (20 mmol) of cyanothioacetamide (IV).
Yield 2.3 g (59%), yellow powder, mp 143–145°C
(from EtOH). IR spectrum, ν, cm–1: 3398, 3302, 3214
1
1
(CONH), 1648 (δNH2). H NMR spectrum, δ, ppm:
(NH2); 2213 (C≡N), 1642 (δNH2). H NMR spectrum,
2.79 s (3H, Me), 6.69 br.s (2H, NH2), 6.85 br.s (2H,
NH2), 7.01 d (1H, 5-H, J = 4.02 Hz), 8.33 d (1H, 6-H,
J = 4.02 Hz). Mass spectrum, m/z (Irel, %): 209 (4)
[M + 2]+, 208 (13) [M + 1]+, 207 (100) [M]+, 190 (88)
[M – NH3]+, 162 (35), 135 (42), 118 (41), 91 (17), 65
(18), 45 (19), 39 (15). Found, %: C 51.99; H 4.25;
N 20.18. C9H9N3OS. Calculated, %: C 52.16; H 4.38;
N 20.27. M 207.25.
δ, ppm: 0.89 t (3H, Me, J = 6.3 Hz), 1.14–1.42 m
(12H, CH2), 1.53–1.66 m (2H, CH2), 2.61 t (2H, CH2,
J = 4.8 Hz), 3.11 t (4H, CH2NCH2, J = 4.52 Hz), 3.75 t
(4H, CH2OCH2, J = 4.52 Hz), 7.96 br.s (2H, NH2);
no N+H2 signal was observed because of fast H/D
exchange. Mass spectrum, m/z (Irel, %): 302 (11)
[Manion + 1]+, 301 (25) [Manion]+, 300 (19) [Manion – 1]+,
273 (18), 259 (38), 245 (46), 232 (44), 217 (61), 204
(70), 203 (100), 190 (82), 177 (14), 145 (16), 103 (15),
88 (91), [Mcation]+, 87 (46) [Mcation – 1]+, 69 (20).
Found, %: C 61.55; H 7.94; N 17.80. C20H31N5OS.
Calculated, %: C 61.66; H 8.02; N 17.98. M 389.56.
9′-Methyl-1′H-spiro[cyclohexane-1,2′-pyrido-
[3′,2′:4,5]thieno[3,2-d]pyrimidin]-4′(3′H)-one (XV).
A mixture of 2.1 g (10 mmol) of thienopyridine XIV
and 1.03 mL (10 mmol) of cyclohexanone in 15 mL of
glacial acetic acid was heated for 2 h under reflux.
After cooling, the precipitate was filtered off and
washed with diethyl ether. Yield 2.2 g (75%), grey
powder, mp 235–237°C (from AcOH); fluoresces
under UV light. IR spectrum, ν, cm–1: 3260, 3174
2-(6-Amino-3,5-dicyano-4-heptylpyridin-2-ylsul-
fanyl)acetamide (XVIIIa) was synthesized as de-
scribed above for compounds XI from 3.6 g (10 mmol)
of salt XVIa and 0.94 g (10 mmol) of chloroacetamide
(XII). Yield 2.5 g (76%), white powder, mp 155–
157°C (from EtOH). IR spectrum, ν, cm–1: 3398, 3330,
3211 (NH2); 2218 (C≡N), 1677 (CONH), 1642
1
(NH); 1714 (CONH). H NMR spectrum, δ, ppm:
1.08–1.35 m (1H), 1.46–1.62 m (7H), and 1.98–2.15 m
(2H) (C6H10), 2.78 s (3H, Me), 5.94 br.s (1H, NH),
7.19 d (1H, Harom, J = 4.2 Hz), 7.93 br.s (1H, NHCO),
8.43 d (1H, Harom, J = 4.2 Hz). Mass spectrum: m/z 288
(Irel 100%) [M + 1]+. Found, %: C 62.55; H 5.80;
N 14.55. C15H17N3OS. Calculated, %: C 62.69; H 5.96;
N 14.62. M 287.38.
1
(δNH2). H NMR spectrum, δ, ppm: 0.87 t (3H, Me,
J = 7.1 Hz), 1.15–1.42 m (8H, CH2), 1.51–1.69 m (2H,
CH2), 2.71 t (2H, CH2, J = 7.2 Hz), 3.84 s (2H, SCH2),
7.22 br.s and 7.52 br.s (1H each, CONH2), 7.96 br.s
(2H, NH2). Mass spectrum: m/z 332 (Irel 100%) [M – 1]+.
Found, %: C 57.86; H 6.25; N 21.00. C16H21N5OS.
Calculated, %: C 57.98; H 6.39; N 21.13. M 331.44.
Morpholinium 6-amino-3,5-dicyano-4-heptyl-
pyridine-2-thiolate (XVIa) was synthesized as de-
scribed above for salts VIII from 1.56 mL (10 mmol)
of octanal (Ig) and 2 g (20 mmol) of cyanothioacet-
amide (IV). Yield 2.5 g (69%), yellow powder,
mp 128–130°C (from EtOH). IR spectrum, ν, cm–1:
3410, 3318, 3195 (NH2); 2220 (C≡N), 1645 (δNH).
1H NMR spectrum, δ, ppm: 0.91 t (3H, Me, J =
6.8 Hz), 1.19–1.48 m (8H, CH2), 1.51 m (2H, CH2),
2.53–2.66 m (6H, CH2, CH2NCH2), 3.76 t (4H,
CH2OCH2, J = 4.48 Hz), 8.02 br.s (2H, NH2); no N+H2
signal was observed because of fast H/D exchange.
Mass spectrum, m/z (Irel, %): 275 (6) [Manion + 2]+, 274
(43) [Manion +1]+, 273 (26) [Manion]+, 245 (40), 232 (49),
217 (68), 204 (71), 203 (100), 190 (82), 146 (15), 91
(11), 87 (39) [Mcation – 1]+, 57 (36). Found, %: C 59.68;
6-Amino-2-benzylsulfanyl-4-heptylpyridine-3,5-
dicarbonitrile (XVIIIb) was synthesized as described
above for compounds XI from 3.6 g (10 mmol) of salt
XVIa and 1.15 mL (10 mmol) of benzyl chloride
(XVII). Yield 2.6 g (70%), white powder, mp 110–
111°C (from EtOH). IR spectrum, ν, cm–1: 3386, 3301,
3215 (NH2); 2219 (C≡N), 1649 (δNH2). H NMR
spectrum, δ, ppm: 0.83 t (3H, Me, J = 5.5 Hz), 1.16–
1.35 m (8H, CH2), 1.48–1.61 m (2H, CH2), 2.66 t (2H,
1
CH2, J = 7.5 Hz), 4.44 s (2H, SCH2), 7.23 t (1H, Harom
,
J = 7.5 Hz), 7.23 t (2H, Harom, J = 7.5 Hz), 7.46 d (2H,
Harom, J = 7.8 Hz), 8.10 br.s (2H, NH2). Mass spec-
trum: m/z 363 (Irel 100%) [M – 1]+. Found, %: C 69.11;
H 6.52; N 15.24. C21H24N4S. Calculated, %: C 69.20;
H 6.64; N 15.37. M 364.51
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

SYNTHESIS OF FUNCTIONALIZED ALKYL-SUBSTITUTED CYCLOHEXANONES
1795
6-Amino-2-benzylsulfanyl-4-nonylpyridine-3,5-
dicarbonitrile (XVIIIc) was synthesized as described
above for compounds XI from 3.9 g (10 mmol) of salt
XVIb and 1.15 mL (10 mmol) of benzyl chloride
(XVII). Yield 2.9 g (74%), white powder, mp 105–
106°C (from EtOH). IR spectrum, ν, cm–1: 3382, 3312,
of allyl bromide (XXI). Yield 2.2 g (68%), yellow
powder, mp 275–277°C (from EtOH). IR spectrum, ν,
cm–1: 3311 (NH), 2217 (C=N), 1722 (C=O), 1666
1
(CONH). H NMR spectrum, δ, ppm: 0.84 d (6H, Me,
J = 6.0 Hz), 1.26 t (3H, Me, J = 6.8 Hz), 1.62–1.79 m
(1H, CHMe2), 2.61 d (2H, CH2, J = 6.7 Hz), 3.64 d
(2H, SCH2, J = 6.4 Hz), 4.15 q (2H, OCH2, J =
6.8 Hz), 5.01 d (1H, CH2=, Jcis = 9.9 Hz), 5.19 d (1H,
CH2=, Jtrans = 16.9 Hz), 5.73–5.94 m (1H, =CH); no
NH signal was observed, presumably due to fast
H/D exchange. Mass spectrum: m/z 321 (Irel 100%)
[M + 1]+. Found, %: C 59.87; H 6.13; N 8.65.
C16H20N2O3S. Calculated, %: C 59.98; H 6.29; N 8.74.
M 320.41.
1
3207 (NH2); 2224 (C≡N), 1648 (δNH2). H NMR
spectrum, δ, ppm: 0.83 t (3H, Me, J = 5.0 Hz), 1.15–
1.26 m (12H, CH2), 1.27–1.31 m (2H, CH2), 2.66 t
(2H, CH2, J = 6.5 Hz), 4.44 s (2H, SCH2), 7.28 t (1H,
Harom, J = 6.95 Hz), 7.23 t (2H, Harom, J = 6.95 Hz),
7.46 d (2H, Harom, J = 7.0 Hz), 7.98 br.s (2H, NH2).
Mass spectrum: m/z 391 (Irel 100%) [M – 1]+. Found,
%: C 70.25; H 7.07; N 14.11. C23H28N4S. Calculated,
%: C 70.37; H 7.19; N 14.27. M 392.56.
REFERENCES
Ethyl 5-cyano-4-isobutyl-6-oxo-2-sulfanylpiper-
idine-3-carboxylate (XXa) was synthesized as
described above for compound IX from 1.1 mL
(10 mmol) of isovaleraldehyde (Id) and 2.94 g
(20 mmol) of CH acid XIX. Yield 1.9 g (66%), yellow
powder, mp 320°C (decomp.; from EtOH). IR spec-
trum, ν, cm–1: 3413 (NH), 2215 (C≡N), 1717 (C=O),
1620 (CONH). 1H NMR spectrum, δ, ppm: 0.87 d (6H,
Me, J = 6.5 Hz), 1.23 t (3H, Me, J = 7.0 Hz), 1.85–
1.99 m (1H, CHMe2), 2.21 d (2H, CH2, J = 7.3 Hz),
4.12 q (2H, OCH2, J = 7.0 Hz), 10.98 br.s (1H, NH);
no SH signal was observed, presumably because of
fast H/D exchange. Mass spectrum: m/z 279 (Irel 100%)
[M – 1]+. Found, %: C 55.58; H 5.69; N 9.85.
C13H16N2O3S. Calculated, %: C 55.70; H 5.75; N 9.99.
M 280.34.
1. Brettle, R., Comprehensive Organic Chemistry,
Barton, D. and Ollis, W.D., Eds., Oxford: Pergamon,
1979, vol. 1. Translated under the title Obshchaya
organicheskaya khimiya, Moscow: Khimiya, 1982, vol. 2,
p. 488.
2. Dyachenko, V.D. and Karpov, E.N., Russ. J. Org. Chem.,
2010, vol. 46, p. 1757; Dyachenko, V.D. and Kar-
pov, E.N., Russ. J. Org. Chem., 2011, vol. 47, p. 1.
3. Dyachenko, V.D. and Karpov, E.N., Russ. J. Gen. Chem.,
2013, vol. 83, p. 1394; Dyachenko, V.D. and Rusa-
nov, E.B., Chem. Heterocycl. Compd., 2004, vol. 40,
no. 2, p. 231; Dyachenko, V.D., Russ. J. Gen. Chem.,
2005, vol. 75, p. 440; Dyachenko, V.D., Russ. J. Gen.
Chem., 2006, vol. 76, p. 282; Dyachenko, V.D. and Cher-
nega, A.N., Russ. J. Org. Chem., 2006, vol. 42, p. 567.
4. Aparicio, F.J.L., Mendoza, P.G., Benitez, F.Z., and Gon-
zales, F.S., Anal. Quim., 1985, vol. 81, p. 5; Kriven’-
ko, A.P. and Sorokin, V.V., Zameshchennye tsiklogeksa-
nony (Substituted Cyclohexanones), Saratov: Saratov.
Gos. Univ., 1999, p. 38.
Ethyl 5-cyano-4-hexyl-6-oxo-2-sulfanylpiperi-
dine-3-carboxylate (XXb) was synthesized as
described above for compound IX from 1.6 mL
(10 mmol) of octanal (Ig) and 2.94 g (20 mmol) of
CH acid XIX. Yield 1.9 g (61%), yellow powder,
mp 330°C (decomp., from EtOH). IR spectrum, ν,
cm–1: 3430 (NH), 2220 (C≡N), 1721 (C=O), 1622
5. Ozols, A.I., Pelcher, Yu.E., Kalme, Z.A., Popelis, Yu.Yu.,
Turovskie, I.V., and Duburs, G.Ya., Chem. Heterocycl.
Compd., 1996, vol. 32, no. 1, p. 52.
1
(CONH). H NMR spectrum, δ, ppm: 0.86 t (3H, Me,
6. Gein, V.L., Gein, N.V., Voronin, E.V., and Kriven’-
ko, A.P., Pharm. Chem. J., 2002, vol. 36, p. 131;
Gein, V.L., Zorin, A.A., Gein, N.V., Voronin, E.V., and
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Gein, V.L., Levandovskaya, E.V., Nosova, N.V., Antono-
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J = 6.9 Hz), 1.17–1.34 m (9H, Me, CH2), 1.42–1.56 m
(2H, CH2), 2.24 t (2H, CH2, J = 8.0 Hz), 4.12 q (2H,
OCH2, J = 6.9 Hz), 11.00 br.s (1H, NH); no SH signal
was observed, presumably because of fast H/D ex-
change. Mass spectrum: m/z 307 (Irel 100%) [M – 1]+.
Found, %: C 58.36; H 6.41; N 8.97. C15H20N2O3S. Cal-
culated, %: C 58.42; H 6.54; N 9.08. M 308.40.
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Ethyl 2-allylsulfanyl)-5-cyano-4-isobutyl-6-oxo-
piperidine-3-carboxylate (XXII) was synthesized as
described above for compound XIII from 2.8 g
(10 mmol) of pyridinone XXa and 0.86 mL (10 mmol)
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