Synthesis, structure, and growth-promoting activity of 1-alkyl-4-(3- naphthyloxyprop-1-ynyl)piperidin-4-ols

Article abstract of DOI:10.1007/s11172-013-0353-1

Alkylation of 1- and 2-naphthols with propargyl bromide in acetone in the presence of potassium carbonate led to prop-2-ynyloxynaphthalenes, which upon reaction with 1-alkyl-piperidin-4-ones under the Favorsky conditions afforded the corresponding tertiary alcohols. 1-Methyl-4-[3-(2-naphthyloxy)prop-1-ynyl] piperidin-4-ol hydrochloride was found to possess a high growth-promoting activity in the concentration of 0.001% upon the pre-sowing treatment of beetroot seeds and potatoes and increase their productivity by -20%.

Full text of DOI:10.1007/s11172-013-0353-1

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Russian Chemical Bulletin, International Edition, Vol. 62, No. 11, pp. 2442—2444, November, 2013
2442
Synthesis, structure, and growthꢀpromoting activity
of 1ꢀalkylꢀ4ꢀ(3ꢀnaphthyloxypropꢀ1ꢀynyl)piperidinꢀ4ꢀols*
M. T. Omirzak,a R. Sh. Erkasov,a B. G. Sukhov,b and T. V. Ganenkob
aL. N. Gumilyov Eurasian National University,
ul. Mirzoyana, 010000 Astana, Republic of Kazakhstan.
Eꢀmail: madi.omirzak@gmail.com
bA. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
1 ul. Favorskogo, 664033 Irkutsk, Russian Federation.
Fax: +7 (3952) 419 346. Eꢀmail: ganenko@irioch.irk.ru
Alkylation of 1ꢀ and 2ꢀnaphthols with propargyl bromide in acetone in the presence of
potassium carbonate led to propꢀ2ꢀynyloxynaphthalenes, which upon reaction with 1ꢀalkylꢀ
piperidinꢀ4ꢀones under the Favorsky conditions afforded the corresponding tertiary alcohols.
1ꢀMethylꢀ4ꢀ[3ꢀ(2ꢀnaphthyloxy)propꢀ1ꢀynyl]piperidinꢀ4ꢀol hydrochloride was found to posꢀ
sess a high growthꢀpromoting activity in the concentration of 0.001% upon the preꢀsowing
treatment of beetroot seeds and potatoes and increase their productivity by ~20%.
Key words: alkylation, alkynylation, naphthyloxypropargylic piperidols, growthꢀpromoting
activity.
Scheme 1
Continuing interest of synthetic chemists to the propꢀ
argylꢀtype compounds HCC—CH2—X— (X = O, N, S,
Se, etc.) is due to their high reactivity, unique synthetic
opportunities, and a wide scope of application of their
derivatives.1—4 In the last years, propargylic compounds
were frequently used to prepare various heterocycles using
Sonogashira reaction and Claisen rearrangement.5 Synꢀ
thesis of triazoles using the "click chemistry" concept is
also under rapid development.6 A propargyl group is
believed to be a key substituent in the synthesis of various
agrochemicals.7
In the present work, we report results on the synthesis
and structure establishment of new naphthyloxyproparꢀ
gylic piperidols (Scheme 1) and study their effect on the
growth and development of beetroots and potatoes.
The known propargyloxynaphthalenes 1 and 2 were
obtained as described earlier.1—4 Their Favorsky reaction
with 1ꢀmethylꢀ and 1ꢀpropylpiperidinꢀ4ꢀones in diethyl
ether in the presence of potassium hydroxide led to
1ꢀalkylꢀ4ꢀ(3ꢀnaphthyloxypropꢀ1ꢀynyl)piperidinꢀ4ꢀols 3—6.
The structure of the compounds synthesized was confirmed
by IR and 1H and 13C NMR spectroscopy.
1ꢀnaphthyl (1, 3, 5); 2ꢀnaphthyl (2, 4, 6)
R = Me (3, 4), Pr (5, 6)
Reagents and conditions: i. BrCH2CCH, K2CO3, acetone,
reflux; ii. 1ꢀalkylꢀ4ꢀpiperidone, KOH, Et2O, 21 C.
signals for the oxymethylene and hydroxyl ( 5.7) protons
are observed around  5.0. The protons of the naphthalene
substituent with a total intensity of seven protons resonate
in the low field. The signals with low intensities characꢀ
teristic of quaternary carbon atoms are present in the
13C NMR spectra: the atoms of the acetylene fragment
resonate at  79 and 92, atom C(4) of the piperidine fragꢀ
ment at  65, the naphthalene atoms Cipso at  155. In
general, the NMR spectra completely agree with the strucꢀ
ture of the compounds synthesized in both the intensities
1H NMR spectra of compounds 3—6 contain three
regions for the proton signals. The protons of the methyl
and propyl substituents, as well as CH2 protons of the
piperidine rings, resonate in the region up to  2.5. The
* Dedicated to Academician of the Russian Academy of Sciences
M. P. Egorov on the occasion of his 60th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2442—2444, Novemer, 2013.
1066ꢀ5285/13/6211ꢀ2442 © 2013 Springer Science+Business Media, Inc.

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1ꢀAlkylꢀ4ꢀ(3ꢀnapthyloxypropꢀ1ꢀynyl)piperidinꢀ4ꢀols Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013 2443
of the corresponding protons in the 1H NMR spectra and
Table 2. Effect of the compounds synthesized on the productivꢀ
ity of potatoa
in the number of signals in the 13C NMR spectra, which is
equal to the number of carbon atoms.
Agentb
Potato harvest/t ha–1
account plot
Addition
to control
In continuation of the search of new plant protection
chemicals, compounds 3—6 were converted to waterꢀsoluble
Nꢀhydrochlorides, which were studied for the influence
on growth and development of beetroots and potatoes.
Under laboratory conditions, the effect of piperidinol
hydrochlorides 3•HCl, 4•HCl, 5•HCl, and 6•HCl on
the sprouting energy and germinating capacity of potato
and beetroot was studied. The concentration of the agents
varied from 1.0 to 0.00001%. The optimal concentrations
of the active compounds found in the laboratory experiꢀ
ments were further used under the field conditions to study
their effect on the growth, development, and productivity
of beetroots and potatoes. Four plots were used for each
culture in the field trials, the account plot area for beetroots
was 10 m2, for potatoes 25 m2. The most indicative data
are given in Tables 1 and 2.
on
(%)
average
/t ha–1
I
II
III
IV
Control
3•HCl
4•HCl
5•HCl
6•HCl
13.8 14.1 14.0 14.1
15.5 15.8 16.2 16.5
16.6 16.9 17.2 17.3
15.0 15.5 16.0 15.1
14.9 15.5 15.2 15.6
14.0
16.0
17.0
15.4
15.3
15.6
—
—
2.0
3.0
1.4
1.3
1.6
14.3
21.4
10.0
9.3
Succinic 15.5 15.7 15.2 16.0
acid
11.4
a
Experimental error P = 3.4%, the least mean difference
HCP0.5 = 0.7 t ha–1
.
b Control was water, the concentration of hydrochlorides 3—6
was 0.001%, the concentration of succinic acid (reference)
was 0.02%.
The results of the field trials show that the treatment of
beetroot seeds with compounds 3•HCl and 4•HCl in
the optimal doses accelerated appearance of shoots by
2—4 days. The plants grown from the seeds treated with
agents in the concentrations of 0.001 and 0.0001% grew
and developed better, that eventually led to the increase in
the beetroot harvest. The highest increase in harvest as
compared to the control (5.1 t ha–1 or 22.2%) was obꢀ
tained by the seed soaking in the solutions of compound
4•HCl with the concentration of 0.001%. Compound
4•HCl at the optimal doses increased productivity of
potatoes by more than 20%, whereas the treatment with
the reference compound (succinic acid) gave an 11% inꢀ
crease in productivity.
Experimental
IR spectra were recorded on a JESꢀ25 Fourierꢀspectrometer
in KBr pellets. 1H and 13C NMR spectra were recorded on
a Bruker DРХꢀ400 spectrometer in DMSOꢀd6 and CDCl3 at room
temperature, using hexamethyldisiloxane ( 0.05) as an internal
standard. High resolution mass spectra were obtained on a Brukꢀ
er FTMS Solarix 7.0T instrument, using electrospray ionization.
Melting points of compounds were determined on Boetius heatꢀ
ing stage. Reaction progress and purity of compounds were monꢀ
itored by TLC on Silufol 60 UV 254 plates.
1ꢀMethylꢀ4ꢀ[3ꢀ(1ꢀnaphthyloxy)propꢀ1ꢀynyl]piperidinꢀ4ꢀol
(3). Potassium hydroxide (2.7 g, 48 mmol) was added to a soluꢀ
tion of 1ꢀ(propꢀ2ꢀynyloxy)naphthalene (1) (2.9 g, 16 mmol) in
diethyl ether (100 mL), and the mixture was stirred for 30 min at
room temperature. Then, a solution of 1ꢀmethylpiperidinꢀ4ꢀone
(1.8 g, 16 mmol) in diethyl ether (20 mL) was added slowly
dropwise. After the reaction reached completion, the mixture
was diluted with water (50 mL), extracted with diethyl ether
(5×25 mL), the combined organic extracts were dried with
K2CO3. After evaporation of the solvent, the residue was recrysꢀ
tallized from a mixture of hexane—benzene (10 mL, 4 : 1) to
obtain product 3 (4.1 g, 88%) as a white powder with m.p.
105—107 C. IR (KBr), /cm–1: 3477, 3053, 2944, 2796, 1596,
1581. 1H NMR (DMSOꢀd6), : 1.67 (m, 2 H, H(3´)); 1.76 (m, 2 H,
H(5´)); 2.08 (s, 3 H, NCH3); 2.13 (m, 2 H, H(2´)); 2.47 (m, 2 H,
H(6´)), 5.08 (s, 2 H, OCH2); 5.68 (s, 1 H, OH); 7.13 (d, 1 H,
H(2), J = 7.6 Hz); 7.48 (t, 1 H, H(3), J = 8.0 Hz, J = 2.7 Hz);
7.53—7.60 (m, 3 H, H(4), H(6), H(7)); 7.93 (d, 1 H, H(5),
J = 8.44 Hz); 8.20 (d, 1 H, H(8) J = 7.6 Hz). 13C NMR (DMSOꢀd6),
: 39.0 (C(3´), C(5´)); 45.8 (NCH3); 52.0 (C(2´), with (6´)); 56.6
(OCH2); 65.0 (C(4´)); 79.3 (C); 91.9 (C); 106.8 (C(2)); 121.0
(C(4)); 121.7. (C(8)); 125.4 (C(9)); 125.8 (C(7)); 126.4 (C(3));
126.9 (C(6)); 127.9 (C(5)); 134.4 (C(10)); 153.0 (C(1)). MS,
m/z: 296.16459 [M]+. C19H22NO2. Calculated: M = 296.16451.
Compounds 4—6 were obtained similarly.
Analysis of the data on biological activity shows that
compound 4•HCl is the most active among those studied.
Table 1. Effect of the compounds synthesized on the productiviꢀ
ty of beetroota
Agentb
Beetroot harvest/t ha–1
account plot on
II III
Addition
to control
(%)
average
/t ha–1
I
IV
Control
3•HCl
4•HCl
5•HCl
6•HCl
Heteroꢀ
auxin
22.7 23.0 23.2 23.1
26.0 27.0 26.5 26.5
27.9 28.2 28.1 28.2
25.0 25.5 25.2 25.1
25.0 25.5 25.1 26.0
25.5 25.8 26.0 25.9
23.0
26.5
28.1
25.2
25.4
25.8
—
—
3.5
5.1
2.2
2.4
2.8
15.2
22.2
19.6
10.4
12.2
a
Experimental error P = 4.0%, the least mean difference
HCP0.5 = 0.8 t ha–1
b Control was water, the concentration of hydrochlorides 3—6 was
.
1ꢀMethylꢀ4ꢀ[3ꢀ(2ꢀnaphthyloxy)propꢀ1ꢀynyl]piperidinꢀ4ꢀol
(4). The yield was 78.4%, m.p. 143—145 C (from hexane). IR
0.001%, the heteroauxin (reference) concentration was 0.06%.

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2444
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 11, November, 2013
Omirzak et al.
(KBr), /cm–1: 3438, 3047, 2939, 2806, 1629, 1560. 1H NMR
(DMSOꢀd6), : 1.65 (m, 2 H C(3´)); 1.75 (m, 2 H, H(5´)); 2.00
(s, 3 H, NCH3); 2.12 (m, 2 H, H(2´)); 2.45 (m, 2 H, H(6´));
4.99 (s, 2 H, OCH2); 5.69 (s, 1 H, OH); 7.26 (dd, 2 H, H(3),
J1 = 8.9 Hz, J2 = 2.3 Hz); 7.41 (s, 1 H, H(1)); 7.44 (m, 1 H,
H(6)); 7.52 (t, 1 H, H(7), J = 7.5 Hz); 7.86 (d, 1 H, H(8),
J = 8.2 Hz); 7.90 (d, 1 H, H(4), J = 7.8 Hz); 7.91 (d, 1 H, H(5),
J = 9.1 Hz). 13C NMR (CDCl3, : 39.0 (C(3´), C(5´)); 45.6
(NCH3); 51.9 (C(2´), C(6´)); 56.1 (OCH2); 65.0 (C(4´)); 79.1
(C); 91.9 (C); 108.3 (C(1)); 119.0 (C(3)); 124.3 (C(6)); 126.9
(C(7)); 127.2 (C(8)); 127.9 (C(5)); 129.1 (C(10)); 129.8 (C(4));
134.4 (C(9)); 155.4 (C(2)). MS, m/z: 296.16588 [M]+. C19H22NO2.
Calculated: M = 296.16451.
4ꢀ[3ꢀ(1ꢀNaphthyloxy)propꢀ1ꢀynyl]ꢀ1ꢀpropylpiperidinꢀ4ꢀol
(5). The yield was 85%, m.p. 99—101 C (from hexane). IR
(KBr), /cm–1: 3436, 3056, 2939, 2827, 1598, 1580. 1H NMR
(DMSOꢀd6), : 0.82 (t, 3 H, CH3, J = 7.4 Hz); 1.31—1.40 (m, 2 H,
NCH2CH2CH3); 1.65 (m, 2 H, H(3´)); 1.76 (m, 2 H, H(5´));
2.10 (t, 2 H, NCH2CH2CH3, J = 7.8 Hz)); 2.15 (m, 2 H, H(2´));
2.51 (m, 2 H, H(6´)); 5.08 (s, 2 H, OCH2); 5.67 (s, 1 H, OH);
7.12 (d, 1 H, H(2), J = 7.6 Hz); 7.47 (t, 1 H, H(3), J = 8.0 Hz);
7.53—7.60 (m, 3 H, H(4), H(6), H(7)); 7.92 (d, 1 H, H(5),
J = 7.0 Hz); 8.19 (d, 1 H, H(8), J = 7.0 Hz). 13C NMR (CDCl3),
: 12.2 (CH3); 19.8 (NCH2CH2CH3); 39.1 (C(5´), C(3´)); 49.9
(C(2´), C(6´)); 56.6 (OCH2); 59.9 (NCH2CH2CH3); 65.6 C(4´));
79.3 (C); 91.9 (C); 106.9 (C(2)); 121.0 (C(4)); 121.8 (C(8));
125.5 (C(9)); 125.8 (C(7)); 126.3 (C(3)); 126.9 (C(6)); 127.9
(C(5)); 134.5 (C(10)); 153.0 (C(1)). MS, m/z: 324.19581 [M]+.
C21H26NO2. Calculated: M = 324.19581.
4ꢀ[3ꢀ(2ꢀNaphthyloxy)propꢀ1ꢀynyl]ꢀ1ꢀpropylpiperidinꢀ4ꢀol
(6). The yield was 75%, m.p. 78—80 C (from hexane). IR (KBr),
/cm–1: 3431, 3056, 2956, 2819, 1629, 1560. 1H NMR (DMSOꢀd6),
: 0.76 (t, 3 H, CH3, J = 7.3 Hz); 1.20—1.33 (m, 2 H,
NCH2CH2CH3); 1.62 (m, 2 H, H(3´)); 1.75 (m, 2 H, H(5´));
1.97 (t, 2 H, NCH2CH2CH3, J = 7.5 Hz); 2.07 (m, 2 H, H(2));
2.49 (m, 2 H, H(6´)); 4.99 (s, 2 H, OCH2); 5.67 (s, 1 H, OH);
7.24 (dd, 1 H, H(3), J1 = 9.0 Hz, J2 = 2.4 Hz); 7.41 (s, 1 H,
H(1)); 7.43 (m, 1 H, H(6)); 7.51 (t, 1 H, H(7), J = 7.1 Hz); 7.84
(d, 1 H, H(8), J = 8.2 Hz); 7.88 (d, 1 H, H(4), J = 8.1 Hz); 7.88
(d, 1 H, H(5), J = 9.1 Hz). 13C NMR (DMSOꢀd6), : 12.1 (CH3);
19.8 (NCH2CH2CH3); 39.1 (C(3´), C(5´)); 49.9 (C(2´), C(6´));
56.1 (OCH2); 59.8 (NCH2CH2CH3); 65.7 (C(4´)); 79.3 (C);
91.9 (C); 108.4 (C(1)); 119.0 (C(3)); 124.3 (C(6)); 126.8 (C(7));
127.2 (C(8)); 127.9 (C(5)); 129.1 (C(10)); 129.8 (C(4)); 134.4
(C(9)); 155.3 (C(2)). MS, m/z: 324.19579 [M]+. C21H26NO2.
Calculated: M = 324.19581.
1ꢀMethylꢀ4ꢀ[3ꢀ(1ꢀnaphthyloxy)propꢀ1ꢀynyl]piperidinꢀ4ꢀol
hydrochloride (3•HCl). Diethyl ether saturated with hydrogen
chloride was added dropwise to a solution of compound 3 (2.9 g,
0.01 mol) in diethyl ether (250 mL) to pH 2. The mixture was
stirred on a magnetic stirrer for 25—30 min. A precipitate was
filtered off and washed with diethyl ether (25 mL) to obtain
hydrochloride 3•HCl (3.1 g, 94%) as a white powder, m.p.
196—198 C.
Similarly were obtained 4•HCl (73%, m.p. 168—170 C,
5•HCl (85%, m.p. 163—165 C) and 6•HCl (78%, m.p.
187—189 C).
Biological trials. Beetroot seeds were soaked in freshly preꢀ
pared solutions. Beetroot seeds soaked in water were used as
a control, a 0.06% aqueous heteroauxin was used as a reference.
The seeds were sprouted in Petri dishes in a thermostat, repeatꢀ
ing trials 6 times. Germinated seeds were counted two times:
first, five days after treatment to determine the sprouting energy,
and second, ten days after to determine the germinating capacity
of seeds.
Potato tubers were used to study the effect of the agents on
the buds awakening. A 0.02% aq. succinic acid was used as
a reference in this case. Potato tubers were sprouted in wet sawꢀ
dust, 20 tubers were used in each trial, repeating each trial four
times.
The authors are grateful to A. A. Tleubaev and A. T.
Aitbaev, employees of the Vegetable Cultivation Technology
and Seedꢀgrowing Laboratory of "Kazakh Research Instiꢀ
tute of Potatoꢀgrowing and Vegetableꢀgrowing" of "Kazaꢀ
groinnovatsiya" Ltd. (Astana), for the carrying out experiꢀ
ments on the growthꢀpromoting activity of the compounds
synthesized.
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Received May 31, 2013;
in revised form September 27, 2013