Synthesis of N-propargylanabasine derivatives by the mannich reaction

Article abstract of DOI:10.1007/s11172-007-0256-0

N-Propargylanabasine derivatives bearing various substituents at the carbon atom of the alkyne fragment were obtained by the reaction of anabasine hydrochloride with terminal alkynes and paraformaldehyde. The reaction proceeded with retention of the C(2) chiral center in anabasine fragment. The by-products of the reaction, including 1,3-diacetylene (the products of dimerization of alkynes) and conjugated vinylacetylenes (the rearrangement products of the Mannich adducts) were isolated and characterized.

Full text of DOI:10.1007/s11172-007-0256-0

Russian Chemical Bulletin, International Edition, Vol. 56, No. 8, pp. 1637—1647, August, 2007
1637
Synthesis of Nꢀpropargylanabasine derivatives by the Mannich reaction*
M. V. Mavrovꢀ and S. G. Zlotin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 137 2944. Eꢀmail: zlotin@ioc.ac.ru
NꢀPropargylanabasine derivatives bearing various substituents at the carbon atom of the
alkyne fragment were obtained by the reaction of anabasine hydrochloride with terminal
alkynes and paraformaldehyde. The reaction proceeded with retention of the C(2) chiral center
in anabasine fragment. The byꢀproducts of the reaction, including 1,3ꢀdiacetylene (the prodꢀ
ucts of dimerization of alkynes) and conjugated vinylacetylenes (the rearrangement products of
the Mannich adducts) were isolated and characterized.
Key words: the Mannich reaction, anabasine, alkaloids, alkynes, βꢀaminoalkynes.
Anabasine ((2S)ꢀ2ꢀ(3ꢀpyridyl)piperidine (1)) is an alꢀ
kaloid component of Anabasis aphylla L..1 It serves as the
blockator of nꢀacetylcholine receptors (nꢀAcChr) and
shows neurotoxic properties toward animals and insects.2
Anabasine salts are widely used as the insecticides,1,3,4 as
the medicines helping to give up smoking, and for the
treatment of cutaneous diseases (eczema, psoriasis, etc.).2,5
A quest of anabasine derivatives, combining both the useꢀ
ful biological activity of natural alkaloid and the miniꢀ
mum harmful side effects is a challenging task.6
the Mannich reaction,16 through the formation of catꢀ
ion C with sp2ꢀhybridized C(2) atom (Scheme 1).
Scheme 1
To obtain the Nꢀsubstituted anabasine derivatives,
alkylation,7—9 acylation,9,10 and phosphorilation4,11 reꢀ
actions are used, as well as the conjugate Michael addiꢀ
tion12 and the Mannich reaction. The latter reaction is
not well investigated. The unsuccessful attempts to inꢀ
volve barbituric acid derivatives13 into it and a few exꢀ
amples of Nꢀpropargylanabasines synthesis with the use
of terminal alkynes14 have been reported. The reactions
were carried out with the assistance of AgI (see Ref. 14a),
CuI (see Ref. 14b,c), and CuII (see Ref. 14d) salts, the
yields of the products did not exceed 32—46% (see
Ref. 14c). The published data did not clarify the area of
application of this reaction, particularly, the possibility to
synthesize the functional derivatives of Nꢀpropargylꢀ
anabasine. The latter can be of interest as the biologically
active substances, since Nꢀpropargylamines are known to
show the various forms of physiological activity.15 There
is no information on stereochemical structure of the prodꢀ
ucts, too. The racemization of the chiral center in anaꢀ
basine in the course of the reaction can not be excluded:
this can result from the isomeric transformations of
iminium cations A and В, the possible intermediates of
In order to elaborate a general method for the syntheꢀ
sis of functional derivatives of anabasine, we for the first
time undertook the systematic investigation of the synꢀ
thetic and stereochemical features of condensation of anaꢀ
basine (1) with paraformaldehyde and terminal alkynes.
In contrast to the earlier published works,14 alkaloid 1 was
generated directly in the reaction media from available
anabasine hydrochloride (1•HCl) by treatment with
AcONa. Acetylene hydrocarbons 2a—d, primary, secondꢀ
ary, and tertiary propargylic alcohols 3a—о and 4a—k,
their acetates 5a—d, containing aliphatic, alicyclic, and
aromatic substituents (Scheme 2), as well as derivatives of
homopropargylic alcohols 6a—c and 7a—c (Scheme 3)
were taken as the alkyne components.
* Dedicated to Academician V. A. Tartakovsky in honor of his
75th anniversary.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1576—1585, August, 2007.
1066ꢀ5285/07/5608ꢀ1637 © 2007 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Mavrov and Zlotin
Scheme 2
Scheme 3
i. Cu2Cl2—AcONa/dioxane
6, 7, 12, 13: R = H (6, 12), Me (7, 13); X = H (a), Ac (b), SiMe3 (c)
R1 = Me, R2 = But (a); R1 + R2 = (CH2)6 (b); R1 = R2 = Ph (c)
under the reaction conditions undergo partial dimerizaꢀ
tion to diacetylenes 14, promotes an increase in the yields
of condensation products 8—13, calculated from anaꢀ
basine hydrochloride (1•HCl).
Copper(I) salts (Cu2Cl2, Cu(OAc)2, and Cu2Br2) were
used as catalysts. The type of the anion and amount of the
catalyst used in the range of 0.2—1.5 equiv. turned out to
have no much effect on the yields of the condensation
products. However, greater excess of the catalyst increases
the yield of the side products of dimerization of alkynes
14a—c (Scheme 3), which makes the target compounds
difficult to isolate. It is reasonable to carry out the reacꢀ
tion in dioxane at 60—70 °C. Addition of solvents of variꢀ
ous polarity (benzene, DMF) does not cause an increase
in the yields of condensation products. The elaborated
procedure enabled us to synthesize Nꢀpropargylanabasine
derivatives 8—11 of various structure in 62—85% yield.
The earlier unknown compounds of terpene 9g—i and
norbornene 9j series are among the synthesized products.
The selectivity of the reaction is defined by the alkyne
structure. The reaction proceeds most smoothly for the
derivatives of acetylene hydrocarbons 2a—d. In case of
propargylic alcohols 3 and 4, the formation of hemiꢀacꢀ
etals and aminals, the minor products of methylenation at
their hydroxy group (signals in the region 4.0—4.6 ppm in
a
—
Cu2Cl2—AcONa/dioxane;
b
—
Ac2O, NEt3,
DMAP/CH2Cl2.
2, 8: R = Pr (a), Bu (b), C5H11n (c), C6H13n (d), Me2CH(CH2)3— (e),
CH2=C(Me)— (f), cyclohexꢀ1ꢀenyl (g), Ph (h), H (i)
3, 9:R = Pr (a), Bu (b), Bui (c), But (d), CH2=C(Me)— (e),
CH2=CH(CH2)2— (f), Me2C=CH(CH2)2— (g),
Me2C(OMe)(CH2)3— (h),
Me2CH(CH2)3CH(Me)(CH2)3CH(Me)(CH2)3— (i),
(j), cycloꢀC3H5 (k), Ph (l), PhCH2 (m), Ph(CH2)2— (n),
4ꢀMeOC6H4(CH2)2— (o)
4, 5, 10, 11: R1 = R2 = H (a), Me (b), Et (f), Pri (g), Ph (j);
R
1 = Me, R2 = Et (c); (R1 + R2) = (CH2)5 (d), R1 = H, R2 = Ph (e);
(CH2)4 (h), (CH2)6 (i)
As a rule, the molar ratio anabasine : paraformꢀ
aldehyde : alkyne in the reaction under study was 1 : 3 : 1.5.
It was also found that an excess of alkynes 2—7, which
1
the H NMR spectra) is observed. These side processes
are less pronounced in the reactions of tertiary alcohols

NꢀPropargylation of Anabazine
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1639
3e—d, 3l—o, and 4c—l, especially, if they contain bulky
substituents R, R1, and R2.
mixture in 4, 6, and 8 h after the reaction begins, have
practically the same [αD] values (230 8°), which indiꢀ
cates that no racemization at C(2) chiral center occurs
under the reaction conditions (see Scheme 1).
The side processes also take place during the reaction
of 1•HCl with paraformaldehyde and homopropargylic
alcohols 6a and 7a (see Scheme 3). According to the
1H NMR data, the yields of condensation products 12a
and 13a did no exceed 70% (40% isolated yield). We
found that it was reasonable to use in the Mannich reacꢀ
tion acetylene alcohols 6a and 7a in form of their acetates
6b and 7b or trimethylsilyl ethers 6c and 7c. After removal
of the protecting groups (trimethylsilyl group was elimiꢀ
nated from trimethylsilyl ethers 12c and 13c by treatment
of the reaction mixture with aq. acid) and flashꢀchromaꢀ
tography, the corresponding condensation products 12b,c
and 13b,c gave the individual alcohols 12a and 13a in
65—70% yield calculated from 1•HCl.
The reaction of methylcyclopropylethynylcarbinol (3k)
with anabasine is a complicated one. Along with the exꢀ
pected product 9k, conjugated 1,3ꢀenyne 15 (a mixture of
Z,Eꢀisomers, ∼1 : 5) was unexpectedly obtained, formaꢀ
tion of which results from the cyclopropylcarbinylꢀ
homoallylic rearrangement,17 occurring even under the
mild conditions of the process.
Products 9a—о, 10a,b, 11a,b, 12a,b, and 13a,b, apꢀ
parently, consist of two diastereomers. However, their
1H NMR spectra contain only one set of signals, excludꢀ
ing compounds 9d,m and 11a. In products 9d,m and 11a
and their corresponding hydrochlorides, only the slight
difference (∆δ 0.01—0.03) between chemical shifts of
diastereotopic protons, located near the asymmetric carꢀ
1
bon atoms is observed. According to the H NMR data,
the ratio of diastereomers is 1 : 1.
In conclusion, the condensation of anabasine hydroꢀ
chloride with paraformaldehyde and terminal alkynes was
systematically studied. The reaction was shown to be a
convenient general method for the synthesis of chiral deꢀ
rivatives of Nꢀpropargylanabasine with various substituꢀ
ents at carbon atom of the alkyne fragment.
Experimental
1
H NMR spectra were recorded on a Bruker DRXꢀ500 specꢀ
Structures of the synthesized condensation products
8—13 and their salts were confirmed by elemental analyꢀ
trometer (500.13 MHz) in DMSOꢀd6 with Me4Si as the internal
standard. UV spectra were recorded on a Specord Mꢀ40 Carl
Zeiss (Jena) spectrophotometer for the ethanol solutions.
IR spectra were recorded on a Specord Mꢀ80 spectrophotoꢀ
meter, for oils as the neat samples, for solids in KBr pellets.
Mass spectra were registered on a Finnigan MAT INCOS 50
instrument (EI, 70 eV) with direct inlet of the sample. Melting
points were determined on the Boetius heating table and were unꢀ
1
sis data, IR, H NMR, and mass spectra. The IR spectra
of these compounds contain the absorption bands of
stretching vibrations of the pyridine ring (1590, 1570 cm–1
)
and ОH group (3250—3410 cm–1). The absorption bands
of acetylene fragment in the region 2190—2250 cm–1 have
low intensities.18 The mass spectra are characterized by
the presence of the molecular peak [M+] and of the strong
(40—100%) fragment ion, corresponding to the eliminaꢀ
corrected. The specific rotation values [α ] (deg mL g–1 dm–1
)
D
with chloroform solutions concentrations C/g (100 mL)–1 were
determined on a PUꢀ7 polarimeter. Monitoring of the reaction
progress was performed by TLC on Silufol (UVꢀ254) plates in
chloroform—methanol—ethyl acetate (9 : 1 : 1) with visualizaꢀ
tion in iodine vapors.
1
tion of pyridine [M+ – C5H4N]. In the H NMR spectra
of the compounds obtained, there are signals of NꢀCH2
groups as ABꢀsystem in the region 2.80—3.20 ppm (J =
16.7—17.2 Hz) and of other hydrocarbon fragments of
the molecules. Most of the synthesized products were
converted to the corresponding hydrochlorides upon treatꢀ
ment with dry HCl in acetone.
The physical and chemical properties of compounds
10b—d, obtained by us in state of noncrystallizing oils,
differ from those described in the literature (in the work,8
they are reported as crystalline substances). However,
there are no NMR spectroscopy data for compounds
10b—d in the paper,8 whereas the synthesized by us subꢀ
stances are unambiguously characterized by spectroscopy
methods and by chemical transformation to Nꢀpropargylꢀ
anabasine 8i (R = H) in the presence of a base (the retro
Favorsky reaction).
Compounds 2e,19a 2f,d, 3k, 4e, 6a, 7a,19b 3a—f,l, 4f—h,19c
3d—j, m—o, and 4i,j 19d were synthesized according to the known
procedures. Commercially available compounds 2a—d,h and
4a—c were used without additional purification. Anabasine
hydrochloride (1•HCl), m.p. 220—222 °C, >99% purity;
(S)ꢀbase, [α ] –82.5 (c 0.6, EtOH).
D
Acetates 5a—d (general procedure). A mixture of the correꢀ
sponding alcohol 4a—d (10 mmol), dry CH2Cl2 (20 mL), acetic
anhydride (1.2 g), triethylamine (5 mL), and 4ꢀDMAP (20 mg)
was kept for 40 h at 22—25 °C, poured into iceꢀcold water, and
extracted with ether. The organic layer was washed with satuꢀ
rated solutions of CuSO4, NaHCO3, and NaCl, dried with
MgSO4. The solvents were evaporated, the residue was dissolved
in nꢀhexane, filtered through Al2O3 (15 g), the filtrate was conꢀ
centrated, and the residue was distilled in vacuo (2 Torr). Acꢀ
1
etates 5a—d were obtained, which, according to H NMR data,
The synthesized condensation products 8—13 are opꢀ
tically active compounds. The high negative angle of roꢀ
tation values [αD] are observed both for the free bases and
for their hydrochlorides 8•HCl—13•HCl and 8g•2HCl.
The samples of compound 8b, taken from the reaction
were identical to the authentic samples (Aldrich), the yields
were 83—90%.
Trimethylsilyl ethers 6c and 7c (general procedure). Chloroꢀ
trimethylsilane (15.0 g, 0.14 mol) was gradually added to a soluꢀ
tion of the corresponding alcohol 6a or 7a (0.1 mol) and dry

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Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Mavrov and Zlotin
pyridine (11.8 g, 0.15 mol) in dioxane (60 mL) at 0—5 °C. The
mixture was stirred for 1 h at 20 °C, then was gently refluxed
for 2 h; the formed pyridine hydrochloride was filtered off and
washed with dioxane (30 mL). The obtained solutions of 6c
or 7c, containing ∼6% of alcohols 6a or 7a (GLC, Biokhromꢀ1,
capillary column with OVꢀ101 as stationary phase, 52 m), were
used for further reactions without additional purification.
Condensation of anabasine hydrochloride (1•HCl) with
paraformaldehyde and terminal alkynes 3—7 (general procedure).
Anabasine hydrochloride (1•HCl) (1.56 g, 7 mmol) was added
in one portion to a preꢀheated to ~60°C mixture of alkynes 3—7
(10—12 mmol), paraformaldehyde (0.6 g, 20 mmol), Cu2Cl2
(0.7 g), AcONa (1.5 g), and dioxane (40 mL). The reaction
mixture was vigorously stirred for 5—8 h at 65—70 °C (TLC
monitoring), concentrated on a rotary evaporator, the residue
was dissolved in benzene (100 mL), filtered off the impurities,
and treated with 3N H2SO4 (in case of 8a—i, with 2 М HCl).
The water layer, containing ammonium salts, was treated with
K2CO3 or aq. NH3, and extracted with benzene—ethyl acetate
(2 : 1) mixture. The extract was sequentially washed with water
and brine, dried with MgSO4, and concentrated. The residue
was dissolved in CH2Cl2 (1—2 mL) and chromatographed on a
column (25×2.5 cm) with SiO2 (25.0—30.0 g), eluent: NH4OH
solution (1%), and MeOH (0—10%) in CН2Cl2. Compounds
8a—h, 9a—o, 10a—d,i, 11a—d (oils) and 10h,j (crystals) were
thus obtained.
piperidine, J = 12.0 Hz, J = 2.6 Hz); 2.89 (d, 1 Н, NCН of
piperidine, J = 10.4 Hz); 2.87, 3.09 (both dt, 1 Н, 1 Н, ≡CCН2N,
J = 17.1 Hz, J = 1.8 Hz); 3.27 (dd, 1 Н, NCH of piperidine, J =
11.3 Hz, J = 2.7 Hz); 7.35 (dd, 1 Н, Н of pyridine, J = 7.8 Hz,
J = 4.8 Hz); 7.68 (dt, 1 Н, Н of pyridine, J = 7.8 Hz, J = 1.6
Hz); 8.46 (dd, 1 Н, Н of pyridine, J = 4.8 Hz, J = 1.2 Hz); 8.47
(d, 1 Н, Н of pyridine, J = 2.2 Hz). MS, m/z (Irel (%)): 256 [M+]
(18), 213 (13), 178 [M+ – C5H4N] (100), 161 (14), 55 (16).
Hydrochloride 8b•HCl, m.p. 99—100 °C, [α ] –100.1
D
(c 0.47, EtOH). Found (%): Cl, 12,68. C17H25ClN2. Calcuꢀ
lated (%): Cl, 12.10.
(2S)ꢀ(–)ꢀNꢀ(Octꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (8c),
light oil, the yield was 80%, [α ] –229.4 (c 0.4). Found (%):
D
N, 10.23. C18H26N2. Calculated (%): N, 10.36. IR, ν/cm–1
:
2930, 2856, 1588, 1576, 1428, 1324, 1126, 1100, 1022, 984, 804,
1
716. H NMR, δ: 0.82 (t, 3 Н, CH3, J = 6.6 Hz); 1.25—1.80
(m, 12 Н, 3 CН2 of piperidine, (CН2)3CН3); 2.16 (t, 2 Н,
≡CCН2CН2, J = 6.6 Hz); 2.48 (t, 1 Н, NCН of piperidine, J =
12.0 Hz); 2.84 (d, 1 Н, NCН of piperidine, J = 10.0 Hz); 2.89,
3.10 (both d, 1 Н, 1 Н, ≡CCН2N, J = 17.0 Hz); 3.29 (d, 1 Н,
NCН of piperidine, J = 11.0 Hz); 7.37 (dd, 1 Н, Н of pyridine,
J = 7.8 Hz, J = 4.8 Hz); 7.68 (br.d, 1 Н, Н of pyridine, J =
7.8 Hz); 8.45 (d, 1 Н, Н of pyridine, J = 4.8 Hz); 8.47 (br.s, 1 Н,
Н of pyridine). MS, m/z (Irel (%)): 270 [M+] (16), 213 (14), 192
[M+ – C5H4N] (100), 161 (20), 105 (15), 79 (14), 55 (28).
A mixture of monoꢀ and dihydrochlorides 8c•HCl and
In case of alkynes 3d, and 4i,j, the benzene solution was
concentrated and, after usual treatment, diacetylene glycols
14а—c were obtained, which were identical to the described
earlier.20
8c•2HCl (20—30%), m.p. 99—100 °C, [α ] –96.4 (c 0.41,
D
EtOH). 1H NMR, δ: 0.89 (t, 3 Н, CH3, J = 6.7 Hz); 1.33, 1.52,
1.62, 1.82—2.03, 2.18 (all m, 4 Н, 2 H, 1 H, 3 H, 2 H, 3 CН2 of
piperidine, (CН2)3CН3); 2.29 (t, 2 Н, ≡CCН2CН2, J = 6.7 Hz);
3.18 and 3.61 (t and d, 1 Н each, 2 NCН of piperidine, J =
12.0 Hz); 3.54, 3.81 (both d, 1 Н each, ≡CCН2N, J = 16.0 Hz);
4.43 (d, 1 Н, NCН of piperidine, J = 12.0 Hz); 7.82, 8.68, 8.81,
9.07 (all br.s, 1 Н each, 4 Н of pyridine); 12.4 (br.s, 1 Н, NH).
(2S)ꢀ(–)ꢀNꢀ(Nonꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (8d),
Anabasine derivatives hydrochlorides 8•nHCl—11•nHCl
(n = 1, 2) (general procedure). A solution of HCl (10%,
0.3—0.4 mL) in dry ether was added to a solution of compounds
8—12 (40—70 mg) in acetone (0.2—0.5 mL). The formed oil
was twice reꢀprecipitated from PriOH (2—6%) solution in orꢀ
ganic solvent (acetone, ethyl acetate, or benzene), dried in vacuo
(1 Torr) at 100—120 °C. Monoꢀ and (or) dihydrochlorides as
amorphous powders were obtained. The yields, physical and
chemical properties, and elemental analysis data for compounds
8—11 and the corresponding hydrochlorides are given below.
(2S)ꢀ(–)ꢀNꢀ(Hexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (8а),
light oil, the yield was 79%, [α ] –217.2 (c 0.4). Found (%):
D
N, 9.74. C19H28N2. Calculated (%): N, 9.85. IR, ν/cm–1: 2932,
2856, 1592, 1576, 1424, 1324, 1128, 1100, 1028, 984, 804, 716.
1H NMR, δ: 0.78 (t, 3 Н, CH3, J = 6.6 Hz); 1.28—1.81 (m, 14 Н,
3 CН2 of piperidine, (CН2)4CН3); 2.19 (t, 2 Н, ≡CCН2CН2,
J = 6.6 Hz); 2.46 (t, 1 Н, NCН of piperidine, J = 12.0 Hz); 2.86
(d, 1 Н, NCН of piperidine, J = 10.0 Hz); 2.89, 3.09 (both d,
1 Н, 1 Н, ≡CCН2N, J = 17.0 Hz); 3.29 (d, 1 Н, NCН of
piperidine, J = 11.0 Hz); 7.37 (dd, 1 Н, Н of pyridine, J =
7.8 Hz, J = 4.8 Hz); 7.68 (br.d, 1 Н, Н of pyridine, J = 7.8 Hz);
8.45 (d, 1 Н, Н of pyridine, J = 4.8 Hz); 8.47 (br.s, 1 Н,
Н of pyridine). MS, m/z (Irel (%)): 284 [M+] (17), 213 (13), 207
(16), 206 [M+ – C5H4N] (100), 161 (16,9), 104 (11.4), 55 (13.7).
A mixture of monoꢀ and dihydrochlorides 8d•HCl and
light oil, the yield was 81%, [α ] –243.2 (c 0.48). Found (%):
D
N, 11.37. C16H22N2. Calculated (%): N, 11.56. IR, ν/cm–1
:
2932, 1592, 1576, 1428, 1324, 1128, 1100, 1024, 984, 804, 716.
1H NMR, δ: 0.94 (t, 3 Н, Me, J = 6.6 Hz); 1.30—1.52 (m, 8 Н,
3 CН2 of piperidine, CН2CН3); 2.16 (t, 2 Н, ≡CCН2CН2, J =
6.6 Hz); 2.43 (t, 1 Н, NCН of piperidine, J = 12.0 Hz); 2.78 (d,
1 Н, NCН of piperidine, J = 10.0 Hz); 2.84, 3.10 (both dt, 1 Н,
1 Н, ≡CCН2N, J = 17.0 Hz, J = 1.8 Hz); 3.29 (dd, 1 Н, NCH of
piperidine, J = 11.3 Hz, J = 2.6 Hz); 7.37 (dd, 1 Н, Н of
pyridine, J = 7.8 Hz, J = 4.8 Hz); 7.68 (br.d, 1 Н, Н of pyridine,
J = 7.8 Hz); 8.44 (d, 1 Н, Н of pyridine, J = 4.8 Hz); 8.49 (br.s,
1 Н, Н of pyridine). MS, m/z (Irel (%)): 242 [M+] (18), 241 (12),
213 (18), 164 [M+ – C5H4N] (100), 161 (15), 79 (14).
8d•2HCl (20—30%), m.p. 85—86 °C, [α ] –84.2 (c 0.5, EtOH).
D
1H NMR, δ: 0.88 (t, 3 Н, CH3, J = 6.6 Hz); 1.18—1.39, 1.49,
1.61, 1.81—1.99, 2.12 (all m, 6 Н, 2 H, 1 H, 3 H, 2 H, 3 CН2 of
piperidine, (CН2)4CН3); 2.34 (t, 2 Н, ≡CCН2CН2, J = 6.6 Hz);
3.17 and 3.61 (t and d, 1 Н each, 2 NCН of piperidine, J =
12.0 Hz); 3.55, 3.82 (both d, 1 Н each, ≡CCН2N, J = 16.0 Hz);
7.89, 8.72, 8.84, 9.09 (all br.s, 1 Н each, 4 Н of pyridine); 12.4
(br.s, 1 Н, NH).
(2S)ꢀ(–)ꢀNꢀ(Heptꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (8b),
light oil, the yield was 84%, [α ] –232.6 (c 0.36). Found (%):
D
N, 10.64. C17H24N2. Calculated (%): N, 10.93. IR, ν/cm–1
:
2928, 2856, 1588, 1576, 1428, 1324, 1126, 1100, 1022, 984,
804, 716. 1H NMR, δ: 0.90 (t, 3 Н, CH3, J = 6.6 Hz); 1.36—1.78
(m, 10 Н, 3 CН2 of piperidine, (CН2)2CН3); 2.20 (tt, 2 Н,
≡CCН2CН2, J = 6.6 Hz, J = 1.8 Hz); 2.44 (dt, 1 Н, NCН of
(2S)ꢀ(–)ꢀ(7ꢀMethyloctꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine
(8е), light oil, the yield was 76%, [α ] –214.7 (c 0.4). Found (%):
D
N, 9.59. C19H28N2. Calculated (%): N, 9.85. IR, ν/cm–1: 2936,
1592, 1576, 1428, 1324, 1228, 1116, 1100, 984, 896, 804, 716.

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1H NMR, δ: 0.88 (d, 6 Н, 2 CH3, J = 6.7 Hz); 1.30, 1.40—1.78
(both m, 3 Н, 8 Н, 3 CН2 of piperidine, (CН2)2CНМе2); 2.48
(t, 1 Н, NCН of piperidine, J = 12 Hz); 2.89 (br.d, 2 Н, NCН of
piperidine, ≡CCННN, J = 17.0 Hz); 3.10 (br.d, 1 Н, ≡CCННN,
J = 17.0 Hz); 3.29 (dd, 1 Н, NCН of piperidine, J = 11.4 Hz,
J = 2.6 Hz); 7.36 (dd, 1 Н, Н of pyridine, J = 7.6 Hz, J =
4.6 Hz); 7.69 (br.d, 1 Н, Н of pyridine, J = 7.6 Hz); 8.46 (t, 2 Н,
2 Н of pyridine, J = 1.4 Hz). MS, m/z (Irel (%)): 284 [M+] (11),
206 [M+ – C5H4N] (100), 161 (19), 105 (10), 55 (12).
A mixture of monoꢀ and dihydrochlorides 8h•HCl and
8h•2HCl (20—30%), m.p. 131—133 °C, [α ] –154.5 (c 0.45,
D
EtOH).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethylheptꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ
(3ꢀpyridyl)piperidine (9а), oil, the yield was 76%, [α ] –205.2
D
(c 0.37). Found (%): N, 9.70. C18H26N2O. Calculated (%):
N, 9.78. IR, ν/cm–1: 3380, 3212, 2936, 1596, 1580, 1432, 1324,
1100, 1028, 716.
Hydrochloride 9a•HCl, m.p. 108—110 °C, [α ] –105.0
D
(2S)ꢀ(–)ꢀNꢀ(4ꢀMethylpentꢀ4ꢀenꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piꢀ
(c 0.44). Found (%): Cl, 11.42. C18H27ClN2O. Calculated (%):
Cl, 10.98. H NMR, δ: 0.96 (t, 3 Н, CH3, J = 6.7 Hz); 1.19 (s,
1
peridine (8f), fast darkening oil, the yield was 64%, [α ] –308.6
D
(c 0.44). Found (%): N, 11.29. C16H20N2. Calculated (%):
3 Н, CН3); 1.17—2.35 (m, 5 Н, 2 CН2 of piperidine, CH of
propyl); 1.92 and 2.18 (m and br.s, 3 Н, 2 Н, CH, CН2 of
propyl, CН2 of piperidine); 3.19, 3.59 (td, 1 Н each, 2 NCН of
piperidine, J = 12.0 Hz); 3.50, 3.82 (both d, 1 Н each, ≡CCН2N,
J = 17.0 Hz); 4.43 (d, 1 Н, NCН of piperidine, J = 12.0 Hz);
4.9 (br.s, 2 Н, NН, OH); 7.87, 8.52, 8.86, 9.01 (all s, 1 Н each,
4 Н of pyridine). MS, m/z (Irel (%)): 286[M+] (10), 208
[M+ – C5Н4N] (100), 161 (23), 105 (15), 78 (10), 43 (64).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethyloctꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀ
N, 11.66. UV (EtOH), λmax/nm (ε): 222 (9800). IR, ν/cm–1
:
2938, 1650, 1594, 1576, 1430, 1170, 1100, 1074, 968, 754, 716.
1H NMR, δ: 1.32—1.78 (m, 6 Н, 3 CН2 of piperidine); 1.87 (s,
3 Н, CН3); 2.44 (td, 1 Н, NCН of piperidine, J = 11.8 Hz,
J = 2.4 Hz); 2.92 (br.d, 1 Н, NCН of piperidine, J = 11.3 Hz);
3.02, 3.26 (both d, 1 Н each, 1 Н, ≡CCН2N, J = 17.5 Hz); 3.28
(dd, 1 Н, NCН of piperidine, J = 11.3 Hz, J = 2.5 Hz); 5.24 (s,
1 Н, =CHН); 5.28 (t, 1 Н, =CНН, J = 1.2 Hz); 7.37 (dd,
1 Н, Н of pyridine, J = 7.8 Hz, J = 4.7 Hz); 7.70 (br.d, 1 Н,
Н of pyridine, J = 7.8 Hz); 8.46 (dd, 1 Н, Н of pyridine,
J = 4.7 Hz, J = 1.5 Hz); 8.48 (d, 1 Н, Н of pyridine,
J = 1.1 Hz). MS, m/z (Irel (%)): 240 [M+] (32), 211 (16), 162
[M+ – C5H4N] (100).
pyridyl)piperidine (9b), oil, the yield was 84%, [α ] –205.3
D
(c 0.36). Found (%): N, 9.46. C19H28N2O. Calculated (%):
N, 9.71. IR, ν/cm–1: 3400, 3220, 2912, 2236 (—C≡C—), 1596,
1
1580, 1432, 1324, 1188, 1100, 984, 808, 716. H NMR, δ: 0.89
(t, 3 Н, CH3, J = 6.6 Hz); 1.33 (s, 3 Н, CН3); 1.31, 1.40—1.80
(two m, 3 Н, 9 Н, 3 CН2 of piperidine, (CН2)3CH3); 2.47, 2.84
(overlapped, 1 Н each, 2 NCН of piperidine); 2.90, 3.11 (both d,
1 Н each, ≡CCН2N, J = 17.3 Hz); 3.34 (br.d, 1 Н, NCН of
piperidine, J = 11.0 Hz); 4.98 (s, 1 Н, OH); 7.34 (dd, 1 Н, Н of
pyridine, J = 7.8 Hz, J = 4.7 Hz); 7.68 (br.d, 1 Н, Н of pyridine,
J = 7.8 Hz); 8.46 (br.d, 1 Н, Н of pyridine, J = 4.7 Hz); 8.50
(br.s, 1 Н, Н of pyridine). MS, m/z (Irel (%)): 300 [M+] (15),
222 [M+ – C5H4N] (100), 105 (15), 55 (21), 43 (98).
Dihydrochloride 8f•2HCl, m.p. 115—117 °C, [α ] –113.2
D
(c 0.43, EtOH). Found (%): Cl, 20.07. C16H22Cl2N2. Calcuꢀ
lated (%): Cl, 22.63.
(2S)ꢀ(–)ꢀNꢀ[3ꢀ(Cyclohexꢀ1ꢀenꢀ1ꢀyl)propꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ(3ꢀ
pyridyl)piperidine (8g), fast darkening oil, the yield was 63%,
[α ] –246.0 (c 0.42). UV (EtOH), λmax/nm (ε): 228 (9600). IR,
D
ν/cm–1: 2932, 2856, 1660, 1592, 1580, 1444, 1432, 1324, 1172,
1
1100, 1076, 968, 756, 716. H NMR, δ: 1.30—1.78 (m, 10 Н,
3 CН2 of piperidine, 2 CН2 of cyclohexene); 2.06 (m, 4 Н,
2 CН2C= of cyclohexene); 2.47 (td, 1 Н, NCН of piperidine,
J = 11.8 Hz, J = 2.4 Hz); 2.88 (br.d, 1 Н, NCН of piperidine,
J = 11.2 Hz); 2.98, 3.23 (both d, 1 Н, 1 Н, ≡CCН2N,
J = 17.4 Hz); 3.27 (dd, 1 Н, NCН of piperidine, J = 11.2 Hz,
J = 2.4 Hz); 6.04 (br.s, 1 Н, CН=), 7.37 (dd, 1 Н, Н of pyriꢀ
dine, J = 7.2 Hz, J = 4.8 Hz); 7.68 (d, 1 Н, Н of pyridine,
J = 7.2 Hz); 8.49 (br.s, 2 Н, 2 Н of pyridine). MS, m/z (Irel (%)):
280 [M+] (41), 279 (26), 202 [M+ – C5H4N] (100), 173 (20),
161 (78), 141 (20), 119 (43), 105 (40), 91 (57), 84 (48), 81 (42),
55 (37), 43 (80).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4,6ꢀdimethylheptꢀ2ꢀynꢀ1ꢀyl)ꢀ
2ꢀ(3ꢀpyridyl)piperidine (9c), oil, the yield was 77%, [α ] –201.6
D
(c 0.50). Found (%): N, 9.52. C19H28N2O. Calculated (%):
N, 9.71. IR, ν/cm–1: 3380, 3220, 2936, 1596, 1580, 1432, 1368,
1324, 1160, 1100, 984, 924, 716. 1H NMR, δ: 0.92 (t, 6 Н, CH3,
J = 6.7 Hz); 1.38 (s, 3 Н, CН3); 1.30, 1.47, 1.52—1.80 (all m,
1 Н, 3 Н, 4 Н, 3 CН2 of piperidine, –CH2CH); 1.83 (m, 1 Н,
CН2CH); 2.49, 2.92 (overlapped, 1 Н each, 2 NCН of piperiꢀ
dine); 2.91, 3.13 (both d, 1 Н each, ≡CCН2N, J = 17.2 Hz);
3.32 (br.d, 1 Н, NCН of piperidine, J = 11.0) Hz; 4.90 (s, 1 Н,
OH); 7.25 (dd, 1Н, Н of pyridine, J = 7.8 Hz, J = 4.6 Hz);
7.69 (br.d, 1 Н, Н of pyridine, J = 7.8 Hz); 8.44 (br.d, 1 Н,
Н of pyridine, J = 4.6 Hz); 8.50 (d, 1 Н, Н of pyridine,
Dihydrochloride 8g•2HCl, m.p. 124—126 °C, [α ] –95.8
D
(c 0.45). Found (%): Cl, 19.51. C19H26Cl2N2. Calculated (%):
Cl, 20.07.
J = 1.7 Hz). MS, m/z (Irel (%)): 300 [M+] (15), 222 [M+
–
(2S)ꢀ(–)ꢀNꢀ(3ꢀPhenylpropꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperiꢀ
C5H4N] (100), 206 (23), 204 (26), 161 (42), 122 (38), 105
(28), 43 (58).
dine (8h), dark oil, the yield was 67%, [α ] –104.8 (c 0.5).
D
Found (%): N, 9.82. C19H20N2. Calculated (%): N, 10.14. IR,
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4,5,5ꢀtrimethylhexꢀ2ꢀynꢀ1ꢀ
yl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9d), oil, the yield was 80%,
ν/cm–1: 3032, 2932, 2228 (—C≡C—), 1600, 1592, 1576, 1492,
1
1428, 1324, 1112, 1100, 1028, 984, 756, 716, 692. H NMR, δ:
[α ] –212.6 (c 0.41). Found (%): N, 9.20. C19H28N2O. Calcuꢀ
D
1.35—1.78 (m, 6 Н, 3 CН2 of piperidine); 2.55 (dd, 1 Н, NCН of
piperidine, J = 11.7 Hz, J = 2.4 Hz); 3.00 (br.d, 1 Н, NCН of
piperidine, J = 11,2 Hz); 3.16, 3.38 (both d, 1 Н each, ≡CCH2N,
J = 17.5 Hz); 3.36 (overlapped, 1 Н, NCН of piperidine); 7.37
(m, 4 Н, Н of pyridine, 3 Н of phenyl); 7.45 (m, 2 Н, 2 Н of
phenyl); 7.75 (dd, 1 Н, Н of pyridine, J = 7.8 Hz, J = 1.2 Hz);
8.47 (dd, 1 Н, Н of pyridine, J = 4.7 Hz, J = 1.5 Hz); 8.54 (d,
1 Н, Н of pyridine, J = 4.7 Hz, J = 1.5 Hz). MS, m/z (Irel (%)):
276 [M+] (36), 275 (18), 198 [M+ – C5H4N] (63), 115 (100).
lated (%): N, 9.33. IR, ν/cm–1: 3230, 2936, 1596, 1580,
1428, 1368, 1324, 1172, 1112, 916, 804, 716. 1H NMR
(DMSOꢀd6/CCl4, 1 : 3), δ: 1.02 (s, 9 Н, But); 1.37*, 1.38*
(both s, 1.5 Н each, CН3), 1.32, 1.52, 1.62—1.85 (all m, 1 Н,
1 Н, 4 Н, 3 CН2 of piperidine); 2.58 (t, 1 H, NCН of piperiꢀ
dine, J = 11.0 Hz); 2.89 (overlapped, 1 H, NCН of piperidine);
2.96, 3.11 (both d, 1 Н each, ≡CCН2N, J = 17.0 Hz); 3.16 (m,
* Signals of diastereotopic protons of two diastereomers (1 : 1).

1642
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Mavrov and Zlotin
1 Н, NCН of piperidine); 4.06 (br.s, 1 Н, OH); 7.25, 7.66, 8.44,
8.52 (all br.s, 1 Н each, 4 Н of pyridine).
1 H, OH); 5.16 (t, 1 Н, CH=, J = 6.6 Hz); 7.34 (dd, 1 H, H of
pyridine, J = 6.2 Hz, J = 4.1 Hz); 7.68 (br.t, 1 Н, Н of pyridine,
J = 6.2 Hz); 8.47 (dd, 1 Н, Н of pyridine, J = 4.1 Hz, J =
1.8 Hz); 8.50 (dd, 1 Н, H of pyridine, J = 6.2 Hz, J = 2.1 Hz).
MS, m/z (Irel (%)): 326 [M+] (1), 248 [M+ – C5H4N] (19),
162 (22), 161 (59), 105 (28), 92 (22), 84 (69), 55 (57), 43
(100), 41 (99).
Hydrochloride 9d•HCl, m.p. 101—103 °C. Found (%):
1
Cl, 10.91. C19H29ClN2O. Calculated (%): Cl, 10.52. H NMR
(DMSOꢀd6/CCl4, 1 : 3), δ: 1.01*, 1.03* (both s, 4.5 Н each,
Вut); 1.40*, 1.43* (both s, 1.5 Н each, CН3); 1.75, 1.98, 2.40
(all m, 1 Н, 3 Н, 2 Н, 3 CН2 of piperidine); 3.29 (q, 1 Н, NCН
of piperidine, J = 10.2 Hz); 3.51*, 3.52*, 3.79*, 3.80* (all d,
0.5 Н each, ≡CCН2N, J = 16.0 Hz); 3.59 (d, 1 Н, NCН of
piperidine, J = 10.2 Hz); 4.68*, 4.71* (both d, 0.5 Н each, NCН
of piperidine, J = 10.2 Hz); 7.85 (q, 1 Н, Н of pyridine,
J = 6 Hz); 8.81 (br.t, 1 Н, Н of pyridine, J = 4.4 Hz); 9.0, 9.18
(both br.s, 1 Н each, 2 Н of pyridine). MS, m/z (Irel (%)):
300[M+] (19), 243 (68), 222 [M+ – C5Н4N] (100), 161 (42), 120
(19), 118 (20), 105 (21), 91 (19), 84 (24), 82 (21), 80 (24), 78
(17), 77 (18), 56 (86), 43 (98), 41 (81).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ8ꢀmethoxyꢀ4,8ꢀdimethylnonꢀ
2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9h), the yield was 67%, oil,
[α ] –186.7 (c 0.54). Found (%): N, 7.59. C22H34N2O2. Calcuꢀ
D
lated (%): N, 7.81. IR, ν/cm–1: 3300, 2936, 1592, 1576, 1428,
1324, 1188, 1172, 1096, 1068, 984, 716, 668. 1H NMR, δ:
1.10 (s, 6 H, CH3); 1.25—1.80 (m, 12 Н, CH2 of piperidine,
CH2CH2CH2); 1.35 (s, 3 H, CН3); 2.48, 2.87 (overlapped,
1 Н each, CН2N); 2.90, 3.14 (both d, 1 Н each, ≡CCН2N, J =
17.2 Hz); 3.08 (s, 3 H, CH3O); 3.32 (br.t, 1 Н, CНN, J =
9.0 Hz); 5.15 (s, 1 H, OH); 7.35 (br.t, 1 Н, Н of pyridine, J =
6.0 Hz); 7.70 (br.t, 1 Н, Н of pyridine, J = 6.0 Hz); 8.46 (d, 1 Н,
H of pyridine, J = 2.1 Hz); 8.49, 8.53 (both s, 0.5 Н each, Н of
pyridine). MS, m/z (Irel (%)): 244 (16), 227 (23), 199 (37),
161 (36), 105 (21), 92 (20), 84 (23), 73 (100), 55 (33), 43
(78), 41 (47).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4,5ꢀdimethylhexꢀ5ꢀenꢀ2ꢀ
ynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9е), the yield was 61%, oil,
[α ] –208.2 (c 0.76). Found (%): N, 9.47. C18H24N2O. Calcuꢀ
D
lated (%): N, 9.85. IR, ν/cm–1: 3240, 2936, 1652, 1596, 1580,
1432, 1368, 1324, 1188, 1100, 904, 716. 1H NMR, δ: 1.31,
1.41—1.78 (both m, 1 Н, 5 Н, CH2 of piperidine); 1.46 (s, 3 H,
CН3); 1.81 (s, 3 H, CH3C=); 2.46 and 2.80 (overlapped,
1 Н each, CН2N); 2.83, 3.14 (both d, 1 Н each, ≡CCН2N, J =
17.5 Hz); 3.28 (dd, 1 H, CHN, J = 11.3 Hz, J = 2.4 Hz); 4.80,
5.23, 5.41 (all s, 1 Н each, =CН2, OH); 7.35 (dd, 1 Н, Н of
pyridine, J = 7.8 Hz, J = 4.8 Hz); 7.69 (dd, 1 Н, H of pyridine,
J = 7.8 Hz, J = 1.2 Hz); 8.43 (dd, 1 Н, Н of pyridine, J = 4.8 Hz,
J = 1.5 Hz); 8.48 (d, 1 Н, Н of pyridine, J = 1.2 Hz). MS,
m/z (Irel (%)): 284 [M+] (3.2), 206 [M+ – C5H4N] (71), 161
(59), 119 (24), 105 (21), 92 (19), 84 (24), 77 (22), 43 (100).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethyloctꢀ7ꢀenꢀ2ꢀynꢀ1ꢀyl)ꢀ
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4,8,12,16ꢀtetramethylheptaꢀ
decꢀ4ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9i), the yield was 76%,
oil, [α ] –133.4 (c 0.64). Found (%): N, 5.61. C31H52N2O.
D
Calculated (%): N, 5.98. IR, ν/cm–1: 3300, 2932, 1652, 1600,
1500, 1464, 1432, 1368, 1324, 1300, 1220, 1176, 1092, 756, 716,
692. 1H NMR, δ: 0.82, 0.84 (both d, 6 H each, CH3, J = 6.6 Hz);
1.02—1.38, 1.40—1.80 (both m, 12 Н, 15 H, CН2 of piperidine,
CH2CH); 1.36 (s, 3 H, CН3); 2.48, 2.88 (overlapped, 1 Н each,
CН2N); 2.90, 3.12 (both d, 1 Н each, ≡CCН2N, J = 17.2 Hz);
3.31 (br.t, 1 H, CHN, J = 9.0 Hz); 5.0 (s, 1 H, OH); 7.32
(br.t, 1 Н, Н of pyridine, J = 6.0 Hz); 7.68 (br.t, 1 Н, Н of
pyridine); 8.45 (d, 1 Н, H of pyridine, J = 2.2 Hz); 8.48 (d,
1 H, Н of pyridine, J = 6.0 Hz). MS, m/z (Irel (%)): M+(–), 390
[M+ – C5H4N] (100), 243 (26), 201 (19), 175 (18), 163 (30),
161 (67), 84 (22), 57 (25), 43 (54).
2ꢀ(3ꢀpyridyl)piperidine (9f), the yield was 72%, oil, [α ] –214.1
D
(c 0.4). Found (%): N, 9.82. C19H26N2O. Calculated (%):
N, 9.78. IR, ν/cm–1: 3240, 2936, 1596, 1580, 1432, 1330, 1190,
1164, 1102, 914, 804, 716. 1H NMR, δ: 1.29, 1.40—1.80 (both m,
1 Н, 7 Н, CH2ꢀof piperidine, CН2CН2C=); 1.37 (s, 3 H, CН3);
2.16—2.33 (m, 2 Н, CН2C=); 2.47, 2.87 (overlapped, 1 Н each,
≡CН2N); 2.90, 3.14 (both d, 1 Н each, ≡CCН2N, J = 17.0 Hz);
4.95 (dt, 1 Н, CН2=, J = 12.0 Hz, J = 1.6 Hz); 5.04 (br.d, 1 Н,
CН2=, J = 17.2 Hz); 5.24 (s, 1 H, OH); 5.83 (dddd, CН=CН2,
J = 17.2 Hz, J = 12.0 Hz, J = 6.8 Hz, J = 6.6 Hz); 7.35 (dd, 1 Н,
Н of pyridine, J = 7.8 Hz, J = 4.8 Hz); 7.69 (dd, 1 Н, Н of
pyridine, J = 7.8 Hz, J = 1.7 Hz); 8.46 (dd, 1 Н, Н of pyridine,
J = 4.8 Hz, J = 1.6 Hz); 8.50 (d, 1 Н, Н of pyridine, J = 1.7 Hz).
MS, m/z (Irel (%)): 298 [M+] (4), 225 (23), 220 [M+ – C5H4N]
(100), 199 (16), 175 (22), 161 (91), 159 (22), 132 (16), 122 (38),
119 (23), 118 (23), 105 (34), 92 (28), 84 (28), 79 (20), 78 (26),
65 (17), 55 (39), 43 (85).
(2S,4´RS)ꢀ(–)ꢀNꢀ[4ꢀHydroxyꢀ4ꢀ(bicyclo[2.2.1]heptꢀ5ꢀenꢀ
2ꢀyl)pentꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ(3ꢀpyridyl)piperidine (9j), the yield was
61%, oil, [α ] –193.4 (c 0.35). Found (%): N, 8.09. C22H26N2O.
D
Calculated (%): N, 8.38. IR, ν/cm–1: 3250, 2936, 2232
(—C≡C—), 1596, 1580, 1432, 1332, 1192, 1172, 1100, 1028,
984, 900, 804, 716, 700. 1H NMR, δ: 1.07—1.94 (m, 13 Н, CН2
of piperidine, CН2, CН); 1.38 (s, 3 Н, CН3); 2.76—3.03 (m,
4 Н, CН2N); 3.14 (m, 1 Н, CНN); 5.12, 5.23 (both s, 1 Н total,
OH); 6.10, 6.22 (two m, 2 Н* total, cycloꢀCH=CH—); 7.36,
7.68, 8.47, 8.50 (all br.s, 1 Н each, Н of pyridine).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀCyclopropylꢀ4ꢀhydroxypentꢀ2ꢀynꢀ1ꢀyl)ꢀ
2ꢀ(3ꢀpyridyl)piperidine (9k), the yield was 41%, oil, [α ] –182.5
D
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4,8ꢀdimethylnonꢀ7ꢀenꢀ2ꢀynꢀ
1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9g), the yield was 74%, oil,
(c 0.7). Found (%): N, 9.74. C18H24N2O. Calculated (%):
N, 9.85. IR, ν/cm–1: 3220, 2936, 1596, 1580, 1428, 1328, 1268,
1
[α ] –178.5 (c 0.62). Found (%): N, 8.40. C21H30N2O. Calcuꢀ
1124, 1100, 1028, 984, 948, 740, 716. H NMR, δ: 0.37, 0.51
D
lated (%): N, 8.58. IR, ν/cm–1: 3300, 2936, 2232 (—C≡C—),
1644, 1592, 1580, 1432, 1368, 1324, 1100, 984, 912, 716.
1H NMR, δ: 1.28, 1.44—1.78 (both m, 1 Н, 7 Н, CH2 of piperiꢀ
dine, CH2CH2CН=); 1.37 (s, 3 H, CН3); 1.59, 1.67 (both s,
3 Н each, CН3C=); 2.16 (m, 2 Н, CН2C=); 2.48, 2.90 (overꢀ
lapped, 1 Н each, CН2N); 2.92, 3.15 (both d, 1 Н each,
≡CCН2N, J = 17.2 Hz); 3.30 (overlapped, 1 Н, CНN); 5.14 (s,
(both m, 3 H and 1 Н, CH2 of cyclopropane), 1.05 (m, 1 Н,
CН of cyclopropane); 1.28, 1.36—1.84 (both m, 1 H, 5 Н, CН2 of
piperidine); 1.43 (s, 3 Н, CН3); 2.46, 2.86 (overlapped, 1 Н each,
CН2N); 2.92, 3.14 (both d, 1 H each, ≡CCH2N, J = 17.6 Hz);
3.28 (t, 1 H, CHN, J = 9.0 Hz); 5.15 (s, 1 Н, OН); 7.37
(dd, 1 Н, Н of pyridine, J = 7.9 Hz, J = 4.8 Hz); 7.71 (br.s,
1 Н, H of pyridine); 8.48, 8.52 (both d, 1 H each, Н of pyridine,
* Signals of diastereotopic protons of two diastereomers (1 : 1).
* Signals of endo/exoꢀisomers in the ratio ~4 : 5.

NꢀPropargylation of Anabazine
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1643
J = 4.8 Hz, J = 1.7 Hz). MS, m/z (Irel (%)): 284 [M+] (23), 267
(19), 224 (38), 206 [M+ – C5H4N] (100), 161 (42), 105 (46), 91
(39), 77 (47), 65 (34), 39 (54).
7.70 (d, 1 Н, Н of pyridine, J = 4.6 Hz); 8.46 (d, 1 H, Н of
pyridine, J = 1.8 Hz); 8.53 (br.s, 1 Н, Н of pyridine).
MS, m/z (Irel (%)): 378 [M+] (37), 360 (17), 307 (25), 300
[M+ – C5Н4N] (61), 244 (31), 243 (57), 201 (59), 187 (39), 161
(78), 121 (100), 105 (28), 84 (21), 78 (16), 77 (23), 43 (47).
(2S)ꢀ(–)ꢀNꢀ(4ꢀHydroxybutꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperiꢀ
dine (10а), oil, containing ∼90% of 10а, the yield was 63%,
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀphenylpentꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ
(3ꢀpyridyl)piperidine (9l), the yield was 63%, oil, [α ] –210.6
D
(c 0.33). Found (%): N, 8.49. C21H24N2O. Calculated (%): N,
8.74. IR, ν/cm–1: 3200, 2936, 1596, 1580, 1560, 1432, 1364,
1
1324, 1176, 1100, 1028, 788, 764, 716, 700. H NMR, δ: 1.30,
[α ] –167.4 (c 0.72).
D
1.51, 1.53—1.79 (all m, 1 Н, 1 H, 4 Н, CH2ꢀof piperidine); 1.66
(s, 3 Н, CН3); 2.52, 2.82 (overlapped, 1 H each, CН2N); 2.98,
3.18 (both d, 1 Н each, ≡CCН2N, J = 17.2 Hz); 3.32 (d, 1 H,
CHN, J = 12.0 Hz); 5.91 (s, 1 Н, ОH); 7.27 (t, 1 Н, Н of
pyridine, J = 7.0 Hz); 7.35 (m, 3 Н, НPh); 7.59 (d, 2 Н, HPh, J =
7.0 Hz); 7.27 (t, 1 H, Н of pyridine, J = 7.0 Hz); 7.07 (br.d, 1 Н,
Н of pyridine, J = 7.0 Hz); 8.49 (m, 2 Н, Н of pyridine). MS,
m/z (Irel (%)): 320 [M+] (31.3), 319 [M+ – Н] (15.3), 242
[M+ – C5H4N] (100), 161 (30), 115 (41), 105 (33), 92 (20), 78
(18), 77 (35), 43 (63).
Hydrochloride 10a•HCl, m.p. 97—99 °C, [α ] –94.6
D
(c 0.56). Found (%): N, 10.24; Cl, 13.52. C14H18N2O•HCl.
1
Calculated (%): N, 10.50; Cl, 13.29. H NMR, δ: 1.33, 1.92,
2.24 (all m, 1 Н, 3 Н, 2 Н, CН2 of piperidine); 3.24 (t, 1 Н,
CН2N, J = 10.0 Hz); 3.58, 3.87 (both d, 1 Н each, CCH2N, J =
17 Hz); 3.62 (d, 1 Н, CН2N, J = 10.0 Hz); 4.14 (s, 2 Н, CН2О);
4.62 (d, 1 Н, CНN, J = 10 Hz); 7.92, 8.84, 8.92, 9.08 (all br.s,
1 Н each, Н of pyridine). MS, m/z (Irel (%)): 230 [M+] (7), 161
(11), 152 [M+ – C5Н4N] (100), 105 (11), 92 (11).
(2S)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethylpentꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyriꢀ
dyl)piperidine (10b), the yield was 67%, oil (cf. Ref. 8: m.p.
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethylꢀ5ꢀphenylpentꢀ2ꢀynꢀ
1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9m), the yield was 59%, oil,
80 °C), [α ] –195.6 (c 0.43). Found (%): N, 10.49. C16H22N2O.
D
[α ] –164.2 (c 0.41). Found (%): N, 8.05. C22H26N2O. Calcuꢀ
Calculated (%): N, 10.84. IR, ν/cm–1: 3240, 2932, 1596, 1580,
1428, 1324, 1228, 1172, 1100, 1028, 952, 716. 1H NMR, δ: 1.30,
1.44—1.77 (both m, 1 Н, 5 Н, CH2 of piperidine); 1.38 (s, 6 Н,
CН3); 2.44 (dt, 1 Н, CН2N, J = 11.8 Hz, J = 2.2 Hz); 2.84
(overlapped, 1 Н, CН2N); 2.87, 3.10 (both d, 1 Н each,
≡CCН2N, J = 17.1 Hz); 3.28 (dd, 1 Н, CНN, J = 11.2 Hz, J =
2.4 Hz); 5.13 (s, 1 Н, OH); 7.37 (dd, 1 Н, Н of pyridine, J =
7.8 Hz, J = 4.8 Hz); 7.72 (br.d, 1 Н, Н of pyridine, J = 7.8 Hz);
8.47 (dd, 1 Н, Н of pyridine, J = 4.8 Hz, J = 1.6 Hz); 8.51 (d,
1 Н, Н of pyridine, J = 1.7 Hz). MS, m/z (Irel (%)): 258 [M+]
(13), 180 [M+ – C5Н4N] (81), 161 (19), 105 (20), 78 (14), 65
(16), 43 (100).
D
lated (%): N, 8.38. IR, ν/cm–1: 3200, 2932, 1596, 1580, 1500,
1432, 1362, 1324, 1172, 1124, 1100, 1062, 752, 716, 700.
1H NMR, δ: 1.28, 1.41—1.77 (both m, 1 Н, 5 Н, CН2 of piperiꢀ
dine); 1.60*, 1.61* (both s, 1.5 Н each, CН3); 2.01 (s, OH),
2.42, 2.79 (both t, 1 Н each, CH2N, J = 10.0 Hz); 2.90 (dd,
1 H, ≡CCH2N, J = 17.0 Hz, J = 2.0 Hz); 3.09—3.28 (m, 4 Н,
CHN, ≡CCH2N, CH2Ar); 7.22—7.38 (m, 6 Н, Н pyridyl, НPh);
7.65* (br.t, 1 Н, Н of pyridine, J = 9.0 Hz); 8.41*, 8.48* (both s,
0.5 Н each, Н of pyridine); 8.47 (s, 1 Н, Н of pyridine). MS,
m/z (Irel (%)): 324 [M+] (1), 316 (14), 298 (40), 243 (22), 225
(22), 161 (59), 155 (17), 105 (18), 92 (22), 91 (68), 84 (19), 65
(26), 43 (100).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethylhexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ
(3ꢀpyridyl)piperidine (10c), the yield was 72%, oil (cf. Ref. 8:
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀmethylꢀ6ꢀphenylhexꢀ2ꢀynꢀ
1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (9n), the yield was 72%, oil,
m.p. 76 °C), [α ] –233.8 (c 0.56). Found (%): N, 10.03.
D
[α ] –160.2 (c 0.67). Found (%): N, 7.99. C23H28N2O. Calcuꢀ
C17H24N2O. Calculated (%): N, 10.29. IR, ν/cm–1: 3320, 3240,
2932, 1596, 1580, 1432, 1368, 1208, 1100, 984, 916, 768, 716.
1H NMR, δ: 0.98 (t, 3 Н, CН3, J = 6.6 Hz); 1.35 (s, 3 Н,
CН3); 1.32, 1.45—1.79 (both m, 1 Н, 7 Н, CН2 of piperidine,
CН2CН3); 2.49 (br.t, 1 Н, CН2N, J = 12.0 Hz); 2.80 (overꢀ
lapped, 1 Н, CН2N); 2.84, 3.13 (both d, 1 Н each, ≡CCН2N,
J = 17.0 Hz); 3.30 (d, 1 Н, CНN, J = 11.0 Hz); 5.13 (s, 1 Н,
OH); 7.37 (dd, 1 Н, Н of pyridine, J = 7.8 Hz, J = 5.4 Hz); 7.72
(br.d, 1 Н, Н of pyridine, J = 7.8 Hz); 8.49, 8.51 (both s,
1 Н each, H of pyridine). MS, m/z (Irel (%)): 272 [M+] (17), 194
[M+ – C5Н4N] (100), 161 (21), 105 (11), 43 (18).
D
lated (%): N, 8.04. IR, ν/cm–1: 3240, 2932, 1596, 1580, 1500,
1432, 1368, 1324, 1172, 1124, 1100, 1068, 1028, 984, 752, 716,
1
700. H NMR, δ: 1.30, 1.46—1.77 (both m, 1 Н, 5 H, CH2 of
piperidine); 1.44 (s, 3 Н, CН3); 1.85 (m, 2 H, CН2CH2Ph);
2.52, 2.92 (overlapped, 1 Н each, CН2N); 2.80 (m, 2 H, CH2Ph);
2.97, 3.19 (both d, 1 Н each, ≡CCН2N, J = 17.2 Hz); 3.35 (d,
1 Н, CНN, J = 12.0 Hz); 5.15 (s, 1 Н, OН); 7.18 (t), 7.22 (d),
7.28 (t) (1 Н, 2 H, 2 Н, НPh, J = 7.0 Hz); 7.34 (dd, 1 H, Н of
pyridine, J = 7.6 Hz, J = 4.4 Hz); 7.68 (d, 1 Н, Н of pyridine,
J = 4.4 Hz); 8.46, 8.54 (both br.s, 1 Н each, Н of pyridine). MS,
m/z (Irel (%)): 348 [M+] (47), 270 [M+ – C5Н4N] (100), 161
(60), 119 (20), 105 (33), 91 (68), 77 (18), 43 (44).
(2S)ꢀ(–)ꢀNꢀ[3ꢀ(1ꢀHydroxycyclohexyl)propꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ(3ꢀ
pyridyl)piperidine (10d), the yield was 86%, oil (cf. Ref. 8: m.p.
(2S,4´RS)ꢀ(–)ꢀNꢀ[4ꢀHydroxyꢀ4ꢀmethylꢀ6ꢀ(4ꢀmethoxyꢀ
phenyl)hexꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ(3ꢀpyridyl)piperidine (9о), the yield
78 °C), [α ] –187.5 (c 0.49). Found (%): N, 9.43. C19H26N2O.
D
Calculated (%): N, 9.78. IR, ν/cm–1: 3320, 2936, 2216
(—C≡C—), 1592, 1580, 1428, 1324, 1112, 1100, 984, 920, 804,
736, 716. 1H NMR, δ: 1.15—1.35, 1.40—1.82 (two m, 2 Н,
14 Н, CH2 of piperidine, CH2 cyclohexane); 2.54 (overlapped,
1 Н, CН2N); 2.88 (d, 1 Н, CН2N, J = 10.4 Hz); 2.95, 3.16
(both d, 1 Н each, ≡CCН2N, J = 17.2 Hz); 3.34 (br.d, 1 Н,
CНN, J = 10.4 Hz); 5.04 (s, 1 Н, OH); 7.34 (dd, 1 Н, Н of
pyridine, J = 7.8 Hz, J = 4.4 Hz); 7.67 (d, 1 Н, Н of pyridine,
J = 7.8 Hz); 8.44 (d, 1 Н, Н of pyridine, J = 4.4 Hz); 8.48 (br.s,
1 Н, Н of pyridine). MS, m/z (Irel (%)): 298 [M+] (18), 221 (14),
220 [M+ – C5Н4N] (100), 161 (27), 105 (15), 78 (83), 77 (26),
51 (24), 38 (32), 36 (79).
was 74%, oil, [α ] –159.3 (c 0.38). Found (%): N, 7.46.
D
C24H30N2O2. Calculated (%): N, 7.40. IR, ν/cm–1: 3260, 2936,
1612, 1584, 1516, 1368, 1324, 1300, 1248, 1176, 1100, 1040,
1
984, 820, 716. H NMR, δ: 1.30, 1.38—1.82 (both m, 1 Н, 5 H,
CH2 of piperidine); 1.35 (s, 3 Н, CН3); 1.80, 2.73 (both m,
2 H each, CН2CH2Ph); 2.95, 3.18 (both d, 1 Н each, ≡CCН2N,
J = 17.2 Hz); 3.34 (d, 1 H, CHN, J = 12 Hz); 3.71 (s, 3 Н,
CH3O); 5.12 (s, 1 Н, OH); 6.72, 7.12 (both d, 2 Н each, HPh
,
J = 7.8 Hz); 7.34 (dd, 1 Н, Н of pyridine, J = 7.8 Hz, J = 4.6 Hz);
* Signals of diastereotopic protons of two diastereomers (1 : 1).

1644
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Mavrov and Zlotin
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀphenylbutꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀ
(2S)ꢀ(–)ꢀNꢀ[3ꢀ(1ꢀHydroxycycloheptyl)propꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ
pyridyl)piperidine (10e), the yield was 61%, oil, [α ] –184.1
(3ꢀpyridyl)piperidine (10i), the yield was 64%, oil, [α ] –97.4
D
D
(c 0.47). Found (%): N, 8.79. C20H22N2O. Calculated (%):
(c 0.36). Found (%): N, 8.61. C20H28N2O. Calculated (%):
N, 8.97. IR, ν/cm–1: 3340, 2936, 1596, 1580, 1432, 1328, 1100,
1028, 716. 1H NMR, δ: 1.28, 1.42—1.84, 1.88 (all m, 1 Н, 15 Н,
2Н, CH2 of piperidine, CH2 of cycloheptane); 2.52, 2.92 (overꢀ
lapped, 1 Н, CН2N); 2.94, 3.14 (both m, 1 Н each, ≡CCН2N,
J = 17.2 Hz); 3.32 (dd, 1 Н, CНN, J = 10.8 Hz, J = 1.7 Hz);
5.02 (s, 1 Н, OH); 7.35 (dd, 1 Н, Н of pyridine, J = 7.8 Hz, J =
4.4 Hz); 7.70 (d, 1 Н, Н of pyridine, J = 7.8 Hz); 8.44 (d, 1 Н,
Н of pyridine, J = 4.4 Hz); 8.50 (br.s, 1 Н, Н of pyridine). MS,
m/z (Irel (%)): 312 [M+] (16); 235 (19); 234 [M+ – C5Н4N]
(100); 161 (24); 115 (38); 105 (51); 77 (51).
N, 9.14. IR, ν/cm–1: 3240, 2932, 1592, 1576, 1428, 1364,
1
1176, 1100, 1028, 764, 716, 700. H NMR (CDCl3), δ: 1.36,
1.58—1.78 (both m, 1 Н, 5 Н, CН2 of piperidine); 2.62 and 3.02
(br.s and d, 1 Н each, CН2N, J = 10.0 Hz); 3.15 and 3.26
(both d, 1 Н each, ≡CCН2N, J = 17.0 Hz); 3.36 (br.s, 1 Н,
CНN); 5.52 (s, 1 Н, CНО); 7.26 (overlapped, 1 Н, Н of pyriꢀ
dine); 7.35, 7.41, 7.57 (tdd, 1 Н, 2 Н, 2 Н, Н arom., J = 7.8 Hz);
7.73 (br.s, 1 Н, Н of pyridine); 8.49 (d, 1 Н, Н of pyridine, J =
4.4 Hz); 8.51, 8.56 (both d, 0.5 Н each, Н of pyridine, J =
1.8 Hz). MS, m/z (Irel (%)): 306 [M+] (16), 228 [M+ – C5Н4N]
(100), 105 (11), 77 (16).
(2S)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4,4ꢀdiphenylbutꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀ
pyridyl)piperidine (10j), the yield was 84%, m.p. 136—137 °C,
Dihydrochloride 10e•2HCl, m.p. 125—126 °C, [α ] –86.5
D
(c 0.45). Found (%): Cl, 18.26. C20H22N2O•2НCl. Calcuꢀ
lated (%): Cl, 18.69.
[α ] –228.8 (c 1.0). Found (%): N, 7.34. C26H26N2O. Calcuꢀ
D
lated (%): N, 7.32. IR, ν/cm–1 (Nujol): 3064, 2924, 1592, 1576,
1488, 1452, 1424, 1380, 1340, 1200, 1132, 1112, 1068, 1020,
764, 744, 720, 708, 688. 1H NMR, δ: 1.28, 1.45—1.86 (both m,
1 Н, 5 Н, CH2 of piperidine); 2.56 (dt, 1 Н, CН2N, J = 11.0 Hz,
J = 1.6 Hz); 2.90 (d, 1 Н, CН2N, J = 11.0 Hz); 3.10, 3.32
(both d, 1 Н each, ≡CCН2N, J = 17.1 Hz); 3.36 (d, 1 Н, CНN,
J = 11.0 Hz); 6.58 (s, 1 Н, OH); 7.23 (t, 2 Н, Н arom., J =
7.0 Hz); 7.32 (t, 5 Н, Н arom., Н of pyridine, J = 7.0 Hz); 7.55
(d, 4 Н, Н arom., J = 8.0 Hz); 7.64 (d, 1 Н, Н of pyridine, J =
7.8 Hz); 8.45 (br.s, 2 Н, Н of pyridine). MS, m/z (Irel (%)):
382 [M+] (26); 381 (16); 305 (22); 304 [M+ – C5Н4N] (100);
161 (31); 115 (53); 105 (58); 91 (18); 77 (52).
(2S)ꢀ(–)ꢀNꢀ(4ꢀEthylꢀ4ꢀhydroxyhexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyriꢀ
dyl)piperidine (10f), the yield was 70%, oil, [α ] –210.1 (c 0.41).
D
Found (%): N, 9.72. C18H26N2O. Calculated (%): N, 9.78. IR,
ν/cm–1: 3200—3400, 2936, 2240 (—C≡C—), 1592, 1580, 1432,
1320, 1212, 1188, 1068, 1028, 892, 844, 808, 768, 716. 1H NMR,
δ: 0.94, 0.96 (both t, 3 Н each, CH3, J = 6.6 Hz); 1.30, 1.45—1.83
(both m, 1 Н, 9 Н, CH2 of piperidine, CH2CH3); 2.47 (overꢀ
lapped, 1 Н, CН2N); 2.86 (d, 1 Н, CН2N, J = 12 Hz); 2.91,
3.16 (both d, 1 Н each, ≡CCН2N, J = 16.8 Hz); 3.32 (dd, 1 Н,
CНN, J = 12 Hz, J = 2.4 Hz); 4.94 (s, 1 Н, OH); 7.37 (dd, 1 Н,
Н of pyridine, J = 7.8 Hz, J = 4.6 Hz); 7.70 (d, 1 Н, Н of
pyridine, J = 7.8 Hz); 8.48 (d, 1 Н, Н of pyridine, J = 4.6 Hz);
8.50 (br.s, 1 Н, Н of pyridine). MS, m/z (Irel (%)): 286 [M+] (8);
208 [M+ – C5Н4N] (65); 161 (26); 118 (16); 78 (20); 77 (25); 65
(33); 55 (38); 51 (34); 41 (100).
A mixture of monoꢀ and dihydrochlorides 10j•HCl and
10j•2 HCl (20—30%), m.p. 136—138 °C, [α ] –101.3 (c 0.36).
D
1H NMR, δ: 1.52, 1.90, 2.14 (all m, 1 Н, 3 Н, 2 Н, CH2 of
piperidine); 3.18 (t, 1 Н, CН2N, J = 11.0 Hz); 3.67 (overlapped,
1 Н, CН2N); 3.69, 3.97 (both d, 1 Н each, ≡CCН2N, J =
17.0 Hz); 4.39 (br.s, 1 Н, CНN); 7.27, 7.36 (both t, 2 Н, 4 Н,
Н arom., J = 7.0 Hz); 7.54, 7.57 (both d, 1 Н each, Н arom., J =
8.1 Hz); 7.69 (t, 1 Н, Н of pyridine, J = 6.8 Hz); 8.44, 8.72, 8.94
(all br.s, 1 Н each, Н of pyridine).
(2S)ꢀ(–)ꢀNꢀ(4ꢀHydroxyꢀ4ꢀisopropylꢀ5ꢀmethylhexꢀ2ꢀynꢀ
1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (10g), the yield was 60%, oil,
[α ] –200.4 (c 0.42). Found (%): N, 8.57. C20H30N2O. Calcuꢀ
D
1
lated (%): N, 8.91. H NMR, δ: 0.91—1.02 (m, 12 Н, CH3);
1.28, 1.50, 1.56—1.78 (all m, 1 Н, 1 Н, 4 Н, CH2 of piperidine);
1.82 (m, 2 Н, CНМе2); 2.55 and 2.89 (br.t and d, 1 Н each,
CН2N, J = 11.0 Hz); 2.97 and 3.19 (both d, 1 Н each, ≡CCН2N,
J = 17.2 Hz); 3.36 (d, 1 Н, CНN, J = 11.0 Hz); 4.50, 4.68, 4.81,
4.92 (all s, 1 Н total, OH); 7.35 (dd, 1 Н, Н of pyridine, J =
7.7 Hz, J = 4.4 Hz); 7.69 (d, 1 Н, Н of pyridine, J = 7.7 Hz);
8.46 (d, 1 Н, Н of pyridine, J = 4.4 Hz); 8.49 (br.s, 1 Н, Н of
pyridine).
(2S)ꢀ(–)ꢀNꢀ(4ꢀAcetoxybutꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piꢀ
peridine (11а), the yield was 66%, oil, [α ] –210.6 (c 0.6).
D
Found (%): N, 10.15. C16H20N2O2. Calculated (%): N, 10.29.
IR, ν/cm–1: 2936, 1748 (ОАc), 1592, 1576, 1428, 1228, 1128,
1
1028, 720. H NMR, δ: 1.32, 1.41—1.76 (both m, 1 Н, 5 Н, of
piperidine); 2.12 (s, 3 Н, CH3CО); 2.46 (t, 1 Н, CН2N, J =
11.8 Hz); 2.92 (d, 1 Н, CН2N, J = 11.0 Hz); 2.97, 3.19 (both d,
1 Н each, ≡CCН2N, J = 17.2 Hz); 3.26 (d, 1 Н, CНN, J =
11.2 Hz); 4.72 (s, 2 Н, CН2О); 7.34 (dd, 1 Н, Н of pyridine, J =
7.4 Hz, J = 4.6 Hz); 7.68 (br.d, 1 Н, Н of pyridine, J = 7.4 Hz);
8.47 (d, 1 Н, Н of pyridine, J = 4.6 Hz); 8.50 (s, 1 Н, Н of
pyridine). MS, m/z (Irel (%)): 272 [M+] (10); 213 (16); 194
[M+ – C5Н4N] (92); 105 (21); 92 (20); 77 (14); 51 (22); 43 (100).
A mixture of monoꢀ and dihydrochlorides 10g•HCl and
10g•2 HCl (20—30%): m.p. 108—110 °C, [α ] –88.6 (c 0.43).
D
(2S)ꢀ(–)ꢀNꢀ[3ꢀ(1ꢀHydroxycyclopentyl)propꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ
(3ꢀpyridyl)piperidine (10h), the yield was 72%, m.p. 110—111 °C,
[α ] –302.8 (c 1.0). Found (%): N, 9.68. C18H24N2O. Calcuꢀ
D
lated (%): N, 9.85. IR, ν/cm–1: 3232, 2920, 1592, 1584, 1452,
1428, 1328, 1308, 1220, 1116, 1096, 1028, 1000, 828, 768, 720.
1H NMR, δ: 1.28, 1.45—1.86 (both m, 1 Н, 13 Н, CH2 of piꢀ
peridine, CH2 of cyclopentane); 2.45 (dt, 1 Н, CH2Н, J = 11 Hz,
J = 1.6 Hz); 2.90 (overlapped, 1 Н, CН2N); 2.93, 3.14 (both d,
1 Н each, ≡CCН2N, J = 17.2 Hz); 3.28 (dd, 1 Н, CНN, J =
10.8 Hz, J = 1.7 Hz); 5.13 (s, 1 Н, OH); 7.36 (dd, 1 Н, Н of
pyridine, J = 7.8 Hz, J = 4.4 Hz); 7.70 (d, 1 Н, Н of pyridine,
J = 7.8); 8.46 (d, 1 Н, Н of pyridine, J = 4.4 Hz); 8.50 (br.s,
1 Н, Н of pyridine). MS, m/z (Irel (%)): 284 [M+] (19); 206
[M+ – C5Н4N] (100); 161 (24); 105 (34); 77 (28).
Hydrochloride 11a•HCl, m.p. 179—183 °C, [α ] –132.8
D
(c 0.49). Found (%): Cl, 11.72. C16H20N2O2•HCl. Calcuꢀ
lated (%): Cl, 11.48.
(2S)ꢀ(–)ꢀNꢀ(4ꢀAcetoxyꢀ4ꢀmethylpentꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyriꢀ
dyl)piperidine (11b), the yield was 73%, oil, [α ] –207.5 (c 0.67).
D
Found (%): N, 9.31. C18H24N2O2. Calculated (%): N, 9.33. IR,
ν/cm–1: 2936, 1744 (ОАc), 1592, 1576, 1428, 1368, 1260, 1244,
1
1136, 956, 716. H NMR, δ: 1.65 (s, 6 Н, CH3); 2.49 (overꢀ
lapped, 1 Н, CН2N); 2.85 (d, 1 Н, CН2N, J = 11.0 Hz); 2.94,
3.16 (both d, 1 Н each, ≡CCН2N, J = 17.1 Hz); 3.32 (d, 1 Н,

NꢀPropargylation of Anabazine
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1645
CНN, J = 11.0 Hz); 7.34 (dd, 1 Н, Н of pyridine, J = 7.4 Hz,
J = 4.6 Hz); 7.69 (d, 1 Н, Н of pyridine, J = 7.4 Hz); 8.46 (d,
1 Н, Н of pyridine, J = 4.6 Hz); 8.50 (s, 1 Н, Н of pyridine).
MS, m/z (Irel (%)): 300 [M+] (21); 257 (23); 241 (43); 240 (62);
239 (31); 225 (40); 222 [M+ – C5Н4N] (100); 175 (18); 162
(80); 161 (70); 105 (19); 77 (23); 43 (50).
2240 (—C≡C—), 1744 (ОАc), 1592, 1580, 1428, 1368, 1324,
1240, 1124, 1100, 1016, 960, 716. H NMR, δ: 0.96 (t, 6 Н,
1
CH3, J = 6.6 Hz); 1.28, 1.45—1.78 (both m, 1 Н, 5 Н, CН2 of
piperidine); 1.88, 1.96 (both m, 2 Н each, CН2CH3); 2.02 (s,
3 Н, CH3CО); 2.52 (overlapped, 1 Н, CН2N); 2.86 (d, 1 Н,
CН2N, J = 11.2 Hz); 2.96, 3.20 (both d, 1 Н each, ≡CCН2N,
J = 17.2 Hz); 3.32 (overlapped, 1 Н, CНN); 7.36 (dd, 1 Н, Н of
pyridine, J = 7.4 Hz, J = 4.6 Hz); 7.69 (br.d, 1 Н, Н of pyridine,
J = 7.4 Hz); 8.46 (br.s, 2 Н, Н of pyridine). MS, m/z (Irel (%)):
328 [M+] (14); 285 (15); 269 (24); 268 (24); 253 (11); 250
[M+ – C5Н4N] (68); 239 (24); 161 (86); 92 (24); 79 (21); 77
(22); 55 (21); 43 (100).
(2S)ꢀ(–)ꢀNꢀ(5ꢀHydroxypentꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piꢀ
peridine (12а). Method А. The product was obtained by the
reaction of anabasine hydrochloride (1•HCl) (1.56 g, 7 mmol)
with paraformaldehyde (0.6 g, 20 mmol) and trimethylsilyl ether
6c (10 mmol), as described above. The yield was 71%, oil,
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀAcetoxyꢀ4ꢀmethylhexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀ
pyridyl)piperidine (11c), the yield was 75%, oil, [α ] –223.6
D
(c 0.37). Found (%): N, 9.30. C19H26N2O2. Calculated (%):
N, 9.26. IR, ν/cm–1: 2936, 2236 (—C≡C—), 1744 (ОАc), 1592,
1576, 1428, 1372, 1324, 1304, 1244, 1112, 984, 940, 720.
1H NMR, δ: 0.98 (t, 3 Н, J = 6.6 Hz); 1.29, 1.46—1.98 (both m,
1 Н, 7 Н, CН2 of piperidine, CН2CH3); 1.62 (s, 3 Н, CH3);
2.04 (s, 3 Н, CH3CО); 2.50 (overlapped, 1 Н, CН2N); 2.85 (d,
1 Н, CН2N, J = 11.0 Hz); 2.96, 3.15 (both d, 1 Н each,
≡CCН2N, J = 17.1 Hz); 3.33 (overlapped, 1 Н, CН2N); 7.36
(dd, 1 Н, Н of pyridine, J = 7.4 Hz, J = 4.6 Hz); 7.70 (d, 1 Н,
Н of pyridine, J = 7.4 Hz); 8.42 (d, 1 Н, Н of pyridine, J =
4.6 Hz); 8.46 (s, 1 Н, Н of pyridine). MS, m/z (Irel (%)): 314 [M+]
(10); 255 (15); 236 [M+ – C5Н4N] (55); 161 (52); 105 (16); 92
(20); 84 (15); 79 (16); 77 (28); 65 (18); 43 (100).
[α ] –179.8 (c 0.62). Found (%): N, 11.19. C15H20N2O. Calcuꢀ
D
1
lated (%): N, 11.47. H NMR, δ: 1.30—1.78 (m, 6 Н, CН2 of
piperidine); 2.34 (t, 2 Н, ≡CCН2 J = 6.8 Hz); 2.45 (dt, 1 Н,
CН2N, J = 10.2 Hz, J = 1.8 Hz); 2.90 (overlapped, 1 Н, CН2N);
2.85, 3.08 (both d, 1 Н each, ≡CCН2N, J = 17.2 Hz); 3.28 (br.d,
1 Н, CНN, J = 10.2 Hz); 3.52 (q, 1 Н, CН2О, J = 6.8 Hz); 4.70
(s, 1 Н, OH); 7.32 (dd, 1 Н, Н of pyridine, J = 7.8 Hz, J =
4.7 Hz); 7.71 (d, 1 Н, Н of pyridine, J = 7.8 Hz); 8.44 (d, 1 Н,
Н of pyridine, J = 4.7 Hz); 8.50 (s, 1 Н, Н of pyridine).
Method B. A mixture of acetate 12b (0.47 g, 1.64 mmol),
K2CO3 (0.40 g, 2.90 mmol), and MeOH (10 mL) was stirred for
4 h at 20 °C (TLC monitoring), filtered, the solvent was evapoꢀ
rated, and the residue was chromatographed on Al2O3. Comꢀ
pound 12а was obtained (310 mg, 77%), which was identical
with that from Method А.
(2S)ꢀ(–)ꢀNꢀ[3ꢀ(1ꢀAcetoxycyclohexyl)propꢀ2ꢀynꢀ1ꢀyl]ꢀ2ꢀ(3ꢀ
pyridyl)piperidine (11d), the yield was 87%, oil, [α ] –210.1
D
(c 0.55). Found (%): N, 7.98. C21H28N2O2. Calculated (%):
N, 8.23. IR, ν/cm–1: 2936, 2856, 2232 (—C≡C—), 1748 (ОАc),
1592, 1560, 1444, 1428, 1368, 1328, 1300, 1264, 1236, 1180,
1100, 964, 716. 1H NMR (CDCl3), δ: 1.36, 1.50—1.92, 2.12
(all m, 2 Н, 12 Н, 2 Н, CН2 of piperidine, CН2 of cyclohexane);
2.04 (s, 3 Н, CH3CО); 2.65 (t, 1 Н, CН2N, J = 11.2 Hz); 2.90
(d, 1 Н, CН2N, J = 11.0 Hz); 3.12 (q, 2 Н, ≡CCН2N, J =
17.0 Hz); 3.42 (d, 1 Н, CНN, J = 11.0 Hz); 7.25 (overꢀ
lapped, 1 Н, Н of pyridine); 7.70 (d, 1 Н, Н of pyridine, J =
7.2 Hz); 8.50, 8.60 (both br.s, 1 Н each, Н of pyridine). MS,
m/z (Irel (%)): 340 [M+] (4.0); 280 (12); 262 [M+ – C5Н4N]
(28); 161 (47); 119 (16); 105 (19); 91 (30); 84 (20); 79 (21); 77
(17); 55 (43); 44 (31); 43 (100).
Dihydrochloride 12a•2HCl, m.p. 144—147 °C, [α ] –102.2
D
(c 0.47). Found (%): Cl, 22.48. C15H20N2O•2HCl. Calcuꢀ
1
lated (%): Cl, 23.03. H NMR, δ: 1.32, 1.95, 2.09 (all m, 1 Н,
3 Н, 2 Н, CН2 of piperidine); 2.41 (t, 2 Н, ≡CCН2, J = 6.6 Hz);
3.11 (t, 1 Н, CН2N, J = 10.0 Hz); 3.52, 3.91 (both d, 1 Н each,
≡CCН2N, J = 16.0 Hz); 3.54 (m, 3 Н, CН2О, CН2N); 4.51 (d,
1 Н, CНN, J = 10.0 Hz); 7.84 (t, 1 Н, Н of pyridine, J =
5.0 Hz); 8.69, 9.08 (both br.s, 1 Н each, Н of pyridine); 7.82 (d,
1 Н, Н of pyridine, J = 5.0 Hz). MS, m/z (Irel (%)): 244 [M+]
(15); 213 (15); 166 [M+ – C5Н4N] (100); 161 (16); 105 (15); 92
(14); 65 (18); 53 (26); 39 (24).
(2S,4´RS)ꢀ(–)ꢀNꢀ(4ꢀAcetoxyꢀ4ꢀphenylpentꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀ
pyridyl)piperidine (11е). The product was synthesized from
carbinol 10e, according to the procedure similar to that for
acetates 5. The yield was 92%, oil, [α ] –196.4 (c 0.52).
D
Found (%): N, 7.93. C22H24N2O2. Calculated (%): N, 8.04. IR,
ν/cm–1: 2936, 2268 (—C≡C—), 1740, 1228 (ОАc), 1592, 1576,
1
1456, 1428, 1372, 1100, 1016, 956, 756, 716, 700. H NMR, δ:
1.25, 1.42—1.78 (both m, 1 Н, 5 Н, CН2 of piperidine); 2.45 (q,
1 Н, CН2N, J = 11.0 Hz); 2.87 (d, 1 Н, CН2N, J = 11.0 Hz);
3.02, 3.25 (both d, 1 Н each, ≡CCН2N, J = 17.2 Hz); 3.24
(overlapped, 1 Н, CНN); 6.44 (s, 1 Н, CНО); 7.35* (sextet,
1 Н, Н of pyridine, J = 3.9 Hz); 7.41 (d, 1H), 7.45 (t, 2 H), 7.55
(d, 2 Н) (Н arom., J = 8.0 Hz); 7.63*, 7.66* (both d, 0.5 Н each,
Н of pyridine, J = 7.6 Hz); 8.38* (br.s, 0.5 Н, Н of pyridine),
8.46* (d, 1 Н, Н of pyridine, J = 4.6 Hz); 8.49* (br.s, 0.5 Н,
Н of pyridine). MS, m/z (Irel (%)): 348 [M+] (27); 289 (29); 288
(14); 270 [M+ – C5Н4N] (100); 161 (39); 128 (53); 127 (26);
117 (22); 115 (27); 105 (26); 92 (22); 78 (13); 77 (19); 43 (60).
(2S)ꢀ(–)ꢀNꢀ(4ꢀAcetoxyꢀ4ꢀethylhexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyriꢀ
dyl)piperidine (11f). The product was synthesized from carbinol
10f, according to the procedure similar to that for acetates 5.
(2S)ꢀ(–)ꢀNꢀ(5ꢀAcetoxypentꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperiꢀ
dine (12b). The product was obtained by the reaction of anaꢀ
basine hydrochloride (1•HCl) (1.56 g, 7 mmol) with paraformꢀ
aldehyde (0.6 g, 20 mmol) and acetate 6b (10 mmol), as deꢀ
scribed above. The yield was 82%, oil, [α ] –210.6 (c 0.6).
D
Found (%): N, 9.63. C17H22N2O2. Calculated (%): N, 9.78. IR,
ν/cm–1: 2936, 1744 (ОАc), 1592, 1580, 1428, 1380, 1324, 1240
1
(ОАc), 1040, 984, 716. H NMR (CDCl3), δ: 1.36, 1.52—1.86
(both m, 1 Н, 5 Н, CН2 of piperidine); 2.09 (s, 3 Н, CH3CО);
2.54 (m, 3 Н, ≡CCН2, CН2N); 2.98 (overlapped, 1 Н, CН2N);
3.02, 3.15 (both d, 1 Н each, ≡CCН2N, J = 17.0 Hz); 4.18 (t,
2 Н, CН2О, J = 6.6 Hz); 7.24 (overlapped, 1 Н, Н of pyridine);
7.69, 8.50, 8.59 (all br.s, 1 Н each, Н of pyridine). MS,
m/z (Irel (%)): 286 [M+] (1); 208 [M+ – C5Н4N] (32); 107 (14);
105 (14); 92 (17); 77 (12); 65 (41); 55 (18); 43 (100).
The yield was 77%, oil, [α ] –203.6 (c 0.6). Found (%): N, 8.44.
D
C20H28N2O2. Calculated (%): N, 8.53. IR, ν/cm–1: 2976, 2936,
Hydrochloride 12b•HCl, m.p. 146—147 °C, [α ] –118.5
D
(c 0.53). Found (%): Cl, 11.35. C17H22N2O2·HCl. Calcuꢀ
* Signals of diastereotopic protons of two diastereomers (1 : 1).
lated (%): Cl, 10.98.

1646
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
Mavrov and Zlotin
(2S,5´RS)ꢀ(–)ꢀNꢀ(5ꢀHydroxyhexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyriꢀ
dyl)piperidine (13а). Method А. The product was obtained by the
reaction of anabasine hydrochloride (1•HCl) (1.56 g, 7 mmol)
with paraformaldehyde (0.6 g, 20 mmol) and trimethylsilyl
ether 7c (10 mmol), as described above. The yield was 64%, oil
J = 6.7 Hz); 7.34 (dd, 1 Н, Н of pyridine, J = 7.4 Hz, J =
4.5 Hz); 7.71, 8.47 (both d, 1 Н each, Н of pyridine); 8.49 (br.s,
1 Н, Н of pyridine).
(2S)ꢀ(–)ꢀNꢀ(Propꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl)piperidine (8i).
A finely triturated mixture of compounds 10b—d (2.0 mmol),
КOH powder (0.11 g, 2.0 mmol), and diethyleneglycol (5 mL)
was heated for 5—7 h at 150—170 °C (15 Torr). The cooled to
20 °C reaction mixture was diluted with ethyl acetate—benzene
(1 : 1) mixture (40 mL) and extracted with 3M HCl (4×3 mL).
The aqueous layer was treated with K2CO3, extracted with benꢀ
zene—ethyl acetate (2 : 1) mixture. The extract was sequenꢀ
tially washed with water and brine, dried with MgSO4, and
concentrated. The residue was dissolved in CH2Cl2 (1—2 mL)
and chromatographed on a column (25×2.5 cm) with SiO2
(25.0—30.0 g). Compound 8i was obtained, the yield was
[α ] –197.4 (c 0.58). Found (%): N, 10.61. C16H22N2O. Calcuꢀ
D
lated (%): N, 10.84. IR, ν/cm–1: 3370, 2936, 2248 (—C≡C—),
1596, 1580, 1432, 1328, 1212, 1116, 1028, 984, 940, 732, 716.
1H NMR, δ: 1.16 (d, 3 Н, CH3, J = 6.6 Hz); 1.28, 1.44—1.80
(both m, 1 Н, 5 Н, CН2 of piperidine); 2.19 (dd, 1 Н, ≡CCН2,
J = 6.6 Hz, J = 1.8 Hz); 2.31 (dd, 1 Н, ≡CCН2, J = 6.6 Hz, J =
1.2 Hz); 2.46 (t, 1 Н, CН2N, J = 11.0 Hz); 2.82 (overlapped,
1 Н, CН2N); 2.86, 3.08 (both d, 1 Н each, ≡CCН2N, J =
17.2 Hz); 3.3 (br.m, 1 Н, CНN); 4.62 (s, 1 Н, OH); 3.76 (m,
1 Н, CНО); 7.32 (dd, 1 Н, Н of pyridine, J = 7.8, J = 4.7 Hz);
7.69 (d, 1 Н, Н of pyridine, J = 7.8 Hz); 8.44 (d, 1 Н, Н of
pyridine, J = 4.7 Hz); 8.49 (s, 1 Н, Н of pyridine). MS,
m/z (Irel (%)): 258 [M+] (23); 213 (28); 180 [M+ – C5Н4N]
(100); 105 (12); 45 (35); 43 (12).
62—67%, m.p. 72 °C, [α ] –225.6 (c 0.43). Found (%): N, 13.73.
D
C13H16N2. Calculated (%): N, 13.99. IR, ν/cm–1: 3296, 2104
(—C≡C—), 2936, 2852, 1592, 1576, 1428, 1324, 1100, 1024,
984, 756, 716. 1H NMR, δ: 1.32, 1.45—1.78 (both m, 1 Н, 5 Н,
CН2 of piperidine); 2.46 (dt, 1 Н, CH2N, J = 11.0 Hz, J =
2.0 Hz); 2.87 (t, 1 Н, ≡CН, J = 2.2 Hz); 2.92, 3.15 (both d,
1 Н each, ≡CCН2N, J = 17.2 Hz); 3.16 (br.d, 1 Н, CН2N, J =
10.0 Hz); 3.29 (dd, 1 Н, CНN, J = 12.0 Hz, J = 1.8 Hz);
7.36 (dd, 1 Н, J = 7.6 Hz, J = 4.4 Hz); 7.70 (d, 1 Н, J = 7.6 Hz);
8.42 (d, 1 Н, J = 4.4 Hz); 8.43 (d, 1 Н, J = 1.6 Hz); MS,
m/z (Irel (%)): 200 [M+] (26); 171 (11); 161 (11); 143 (15); 131
(14); 123 (26); 122 [M+ — C5H4N] (100); 105 (46); 92 (27); 65
(35); 55 (34).
Method B. A mixture of acetate 13b (0.45 g, 1.50 mmol),
K2CO3 (0.35 g, 2.54 mmol), and MeOH (10 mL) was stirred for
4 h at 20 °C (TLC monitoring) and filtered, the solvent was
evaporated, the residue was chromatographed on Al2O3. Comꢀ
pound 13а (300 mg, 77%) was obtained, which was identical to
that from Method А.
(2S,5´RS)ꢀNꢀ(5ꢀAcetoxyhexꢀ2ꢀynꢀ1ꢀyl)ꢀ2ꢀ(3ꢀpyridyl) piperiꢀ
dine (13b). The product was obtained by the reaction of anaꢀ
basine hydrochloride (1•HCl) (1.56 g, 7 mmol) with paraformꢀ
aldehyde (0.6 g, 20 mmol) and acetate 7b (10 mmol), as deꢀ
Authors are grateful to N. I. Simirskaya and
A. A. Zhigareva for the help in preparation of the manuꢀ
script.
The work is financially supported in part by the
"Chemical Block Ltd." and ZAO "IꢀBꢀScreen".
scribed above. The yield was 74%, oil, [α ] –208.9 (c 0.5).
D
Found (%): N, 9.13. C18H24N2O2. Calculated (%): N, 9.33. IR,
ν/cm–1: 1746, 1240 (ОАc). 1H NMR (CDCl3), δ: 1.34* (t, 3 Н,
CH3, J = 6.6 Hz); 1.36, 1.51—1.86 (both m, 5 Н, CН2 of piperiꢀ
dine); 2.07 (s, 3 Н, CH3CО); 2.46 (m, 2Н, ≡CCН2); 2.54 (t,
1 Н, CН2N, J = 11.0 Hz); 2.96 (br.d, 1 Н, CН2N, J = 11.0 Hz);
3.04, 3.14 (both d, 1 Н each, ≡CCН2N); 3.29 (d, 1 Н, CНN, J =
11.0 Hz); 5.01 (quintet, 1 Н, CНО, J = 6.6 Hz); 7.24 (overꢀ
lapped, 1 Н, Н of pyridine); 7.64 (d, 1 Н, Н of pyridine, J =
7.6 Hz); 8.49 (d, 1 Н, Н of pyridine, J = 4.6 Hz); 8.57 (br.s,
1 Н, Н of pyridine). MS, m/z (Irel (%)): 300 [M+] (7); 222
[M+ – C5Н4N] (46); 161 (24); 79 (20); 77 (18); 43 (100).
(2S)ꢀ(–)ꢀNꢀ[7ꢀHydroxyꢀ4ꢀmethylheptꢀ4(Е)ꢀenꢀ2ꢀynꢀ1ꢀyl]ꢀ
2ꢀ(3ꢀpyridyl)piperidine (15). The product was obtained by the
reaction of anabasine hydrochloride (1•HCl) (1.56 g, 7 mmol)
with paraformaldehyde (0.6 g, 20 mmol) and 3ꢀcyclopropylbutꢀ
1ꢀynꢀ3ꢀol (3k) (10 mmol), as described above. The formed mixꢀ
ture of compounds 9k and 15 was separated by column chromaꢀ
tography on silica gel. The less polar fractions were chromatoꢀ
graphed twice with light petroleum—CH2Cl2 (from 10 : 1 to 2 : 1)
as the eluent. Compound 15 (0.23 g, 12%) was isolated, oil,
References
1. A. P. Orekhov, Khimiya alkaloidov rastenii SSSR [Chemistry
of Alkaloids of Plants of USSR], Moscow, 1965, 46 (in
Russian).
2. Bol´shaya meditsinskaya encyclopediya [Large Medical
Encyclopaedia], Mеdgiz, Moscow, 1956, 1, 1026 (in Russian).
3. (a) A. S. Sadykov, Khimiya alkaloidov Anabasis aphylla
[Chemistry of Alkaloids of Anabasis Aphylla], Tashkent, Akad.
Nauk Uzbek SSR, 1956 (in Russian); (b) I. Schmeltz, in
Naturally Occuring Insecticides; Eds M. Jacobson and D. G.
Crosby; Marcel Dekker, New York, 1971, 99.
4. A. M. Gazaliev, M. Zh. Zhurinov, Z. Tylyabaev, D. N.
Dalimov, K. D. Mukanova, and S. A. Dyusembaev, Khimiya
Prirodn. Soedinenii, 1989, 584 [Chem. Natural Comp., 1989,
502 (Engl. Transl.)].
5. M. D. Mashkovskii, Lekarstvennye sredstva [Medicines],
Novaya volna, Moscow, 2003, 1, 130 (in Russian).
6. (a) G. A. Cordell, Introduction to Alkaloids, Wiley —
Interscience, New York, 1981; (b) A. M. Gazaliev, M. Zh.
Zhurinov, and S. D. Fazylov, Novye bioaktivnye proizvodnye
alkaloidov [New Bioactive Derivatives of Alkaloids], AlmaꢀAta,
Gylym, 1992, 208 pp. (in Russian); (c) S. W. Szczepanski
and K. G. Anouna, Tetrahedron Lett., 1996, 8841; (d) A. G.
Dobren´kov, Z. Tilyabaev, D. N. Dalimov, and A. A.
[α ] –236.0 (c 0.57). Found (%): N, 9.61. C18H24N2O. Calcuꢀ
D
lated (%): N, 9.85. IR, ν/cm–1: 3240, 2932, 1660, 1592, 1580,
1432, 1324, 1172, 1100, 1076, 968, 756, 716. 1H NMR (CDCl3),
δ: 1.34, 1.43—1.88 (both m, 1 Н, 5 Н, CН2 of piperidine); 1.85
(s, 3 Н, CH3); 2.68 (q, 2 Н, ≡CCН2, J = 6.7 Hz); 2.54 (overꢀ
lapped, 1 H, CН2N); 2.92 (d, 1 Н, CН2N, J = 11.0 Hz); 3.16,
3.34 (both d, 1 Н each, ≡CCН2N, J = 16.8 Hz); 3.35 (overꢀ
lapped, 1 H, CН2N); 3.67 (t, 2 Н, CН2О, J = 6.7 Hz); 5.55 (t,
1 Н, (E)ꢀCH=, J = 6.7 Hz); 5.61 (t, 0.05 Н, (Z )ꢀCH=,
* Signals of diastereotopic protons of two diastereomers (1 : 1).

NꢀPropargylation of Anabazine
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1647
Abduvakhabov, Khimiya prirodn. soedinenii, 1988, 97 [Chem.
Natural Comp., 1988 (Engl. Transl.)].
13. K. A. Krasnov, A. S. Gorovoi, and V. G. Kartsev, in the
book Azotistye Geterotsikly and Alkaloidy [Nitrogen Heteroꢀ
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Received March 21, 2007;
in revised form March 27, 2007