A study of 2-piperidino-1-ethanol and its derivatives as antimicrobial additives to oils

Article abstract of DOI:10.1134/S1070427209090134

Some derivatives of 1-hydroxy-2-pyperidinoethane were studied as antimicrobial additives to lubricant oils.

Full text of DOI:10.1134/S1070427209090134

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 9, pp. 1577–1581. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © S.A. Gamzaeva, P.Sh. Mamedova, K.M. Allakhverdieva, G.Kh. Velieva, M.A. Akhundova, M.A. Allakhverdiev, 2009, published in
Zhurnal Prikladnoi Khimii, 2009, Vol. 82, No. 9, pp. 1479–1483.
ORGANIC SYNTHESIS AND INDUSTRIAL
ORGANIC CHEMISTRY
A Study of 2-Piperidino-1-ethanol and Its Derivatives
as Antimicrobial Additives to Oils
S. A. Gamzaevaa, P. Sh. Mamedovab, K. M. Allakhverdievaa,
G. Kh. Velievaa, M. A. Akhundovaa, and M. A. Allakhverdieva
a Baku State University, Baku, Azerbaijan
b Kuliev Institute of Additive Chemistry, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
Received October 31, 2008
Abstract—Some derivatives of 1-hydroxy-2-pyperidinoethane were studied as antimicrobial additives to
lubricant oils.
DOI: 10.1134/S1070427209090134
Piperidine fragments contained in various organic
compounds exhibit a high physiological activity and
N−CH2CH2OH + RCOCl
are used in medical practice as analgesics and
anesthetics [1]. They are also contained in various
alkaloids, such as anabasine, morphine, bobeline, and
NCH2CH2OC(O)R
−NaCl
II, III
tropine [2]. Piperidine derivatives containing hydroxy
groups in their molecule are used in pharmacology of
neuroleptics and analgesics.
R = CH3 (II), C6H5 (III).
In continuation of studies on the synthesis and
examination of some amino alcohol derivatives in
To expand the assortment of biocide additives to
order to analyze the relationship between their
oils and to examine the dependence of their functional
structure and functional properties [3–8], we syn-
properties on their structure, we reacted 2-piperidino-
thesized 2-piperidino-1-ethanol by reacting piperidine
1-ethanol with various alkyl halides to obtain quarter-
nary salts IV–VI:
with 2-chloro-1-ethanol at 100°C within of 6 h at a
reagent ratio of 2 : 1:
N−CH2CH2−OH + RX
2
NH + ClCH2CH2OH
+
NCH2CH2OH X−
N−CH2CH2OH +
NH⋅HCl
R
IV−VI
I
R = (CH3)2CH, X = I (IV); R = n-C4H9, X = Br (V); R = n-
C5H11, X = Br (VI).
In acylation of 2-piperidino-1-ethanol with acetyl
and benzyl chlorides in the presence of sodium
hydroxide in a solution of carbon tetrachloride, the
corresponding amino esters II and III were
synthesized:
Chlorination of 2-piperidino-1-ethanol I with
thionyl chloride yields 2-piperidinoethyl chloride VII:
1577

1578
GAMZAEVA et al.
The physicochemical constants of the compounds
N−CH2CH2−OH + SOCl2
synthesized are listed in Table 1. The composition and
structure of the compounds were confirmed by IR and
1H and 13C NMR spectroscopy and by elemental
analysis (Table 1).
NCH2CH2Cl + SO2 + HCl
−NaCl
VII
A broad absorption band at 3370–3380 cm–1,
characteristic of stretching vibrations of the primary
hydroxy group, was found in the IR spectrum of the
synthesized 2-piperidinoethanol I. The IR spectra of
amino esters II and III contain no absorption bands at
3370–3380 cm–1, associated with stretching vibrations
of the hydroxy group of the starting amino alcohol, but
there appears a strong absorption band at 1735 cm–1,
characteristic of the C=O bond. The absorption band at
1225 cm–1 corresponds to stretching vibrations of the
C–O bond.
An attempt to synthesize 2-piperidinoethyl chloride
VII by reacting piperidine with 1,2-dichloroethane
failed. The reaction product formed in this case was
1,2-bispiperidinoethane VIII:
NH + ClCH2CH2Cl
N−CH2CH2 N
−2HCl
VIII
1
In the H NMR spectrum of 2-piperidinoethanol I,
The reactions of 1,2-bispiperidinoethane VIII with
various alkyl halides yield bisquaternary salts:
two protons of a methylene group in the piperidine
ring appear in a strong field as a triplet with a chemical
shift centered at 1.4–1.6 ppm. Signals of four protons
of two methylene groups in the piperidine ring were
also observed as a triplet at 1.6–1.7 ppm. Signals of six
protons in the N(CH2)3 moiety appear as a triplet at
2.4–2.6 ppm. Two protons bound to oxygen in the
OCH2 moiety were observed in a comparatively weak
field as a triplet at 3.6–3.8 ppm. The proton of the
hydroxy group appears as a singlet in a weak field at
4.95 ppm.
N−CH2CH2 N
+ 2RX
2X−
+
+
N−CH2CH2 N
R
R
IX−XI
R = (CH3)2CH, X = Br (IX); R = C4H9, X = Br (X); R =
C5H11, X = Br (XI).
Table 1. Physicochemical constants of compounds I–XI
mp, оС
Found, %
Compound
no.
or bp, оС (p, mm Hg)
nD20
Yield, %
C
H
N
64 (1)
69–70 (1)
200–202
fluid
1.3725
1.4650
–
75
80
78
66
70
73
75
85
67
69
73
66.01
63.18
72.37
40.28
49.59
51.49
57.01
73.53
40.45
51.13
53.12
11.78
9.98
8.39
73.77
9.11
9.32
9.50
12.38
7.29
8.96
9.32
11.01
8.27
6.38
4.70
5.38
5.09
9.51
14.42
5.38
6.00
5.78
I
II
III
IV
V
1.4785
–
190–191
80
–
VI
VII
VIII
IX
X
76 (10)
100–102 (1)
200
1.4115
1.4863
180
150
XI
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 9 2009

A STUDY OF 2-PIPERIDINO-1-ETHANOL AND ITS DERIVATIVES
1579
Table 1. (Contd.)
Calculated, %
Formula
Compound
no.
Rf
C
H
N
C7H15NO
65.07
63.13
72.07
40.11
49.63
51.43
56.94
73.41
40.31
51.07
53.02
11.70
10.01
8.21
7.35
9.09
9.35
9.56
12.32
7.09
9.00
9.30
10.84
8.18
6.00
4.67
5.26
5.00
9.49
14.27
5.22
5.96
5.62
0.69
0.55
0.67
0.42
0.33
0.34
0.71
0.63
0.44
0.30
0.46
I
C9H17NO2
C14H19NO2
C10H22INO
C11H24BrNO
C12H26BrNO
C7H14ClN
II
III
IV
V
VI
VII
VIII
IX
X
C12H24N2
C18H38N2I2
C20H42Br2N2
C22H46Br2N2
XI
The following peaks were found in the 13C NMR
spectrum of 2-piperidinoethanol I in accordance with
the electronic structure of carbon: 24, 26.54, and
A study of the antimicrobial properties of
compounds I–XI in an M-10 lubricant oil demon-
strated (Table 2) that, taken in concentrations of 0.5–
1 wt %, they effectively suppress the growth of
microorganisms (bacteria and fungi) attacking this oil.
All the compounds except IV exhibit effective
fungicide properties. Apparently, this property is
imparted by a piperidine ring present in their
molecules. Introduction of an ester group into the
molecule of amino alcohol I (compound III) enhances
its biocide activity. It should be noted that quaternary
salts of 2-piperidinoethanol with alkyl halides exhibit
effective bactericide properties, whereas the bisque-
ternary salts of 1,2-bispiperidinoethane, IX and X
possess only fungicide properties. The data on the
antimicrobial properties of the compounds synthesized
make it possible to recommend use of these com-
pounds as biocide additives to lubricant oils to
preclude their biodegradation.
1
58.61 ppm. In the H NMR spectrum of 1-acetoxy-2-
piperidinoethyl acetate II there appears, in contrast to
the spectrum of the starting amino alcohol I, a strong
singlet at 1.85 ppm, which corresponds to three
protons in the acetyl radical. In the case of amino
benzoate III, protons of the phenyl ring appear as a
multiplet at 7.2–7.8 ppm.
The broad absorption band at 3370–3380 cm–1,
characteristic of the hydroxy group, was not observed
in the IR spectrum of 1,2-bispiperidinoethane. The
signal of the proton of the hydroxy group at 4.95 ppm
1
was not observed in the H NMR spectrum, either.
However, four protons of two methylene groups
appear as a triplet at 1.5 ppm. Signals of eight protons
belonging to four methylene groups in the piperidine
ring were observed at 1.65 ppm. Signals of eight
protons of two N(CH2)2 moieties were observed as a
multiplet at 2.45 ppm. Signals of four protons of two
methylene groups belonging to a piperidine ring were
observed as a singlet at 2.52 ppm. The assignment of
the signals is confirmed by the integral curve.
EXPERIMENTAL
The course of the reactions was monitored and the
individual nature of the products was verified by thin-
layer chromatography on a fixed silica gel layer
1
(Silufol). H NMR spectra were recorded with a
The NMR spectra of other quaternary salts, IX–XI,
of the starting amino alcohol I and 1,2-bispiperi-
dinoethane VIII are similar to the spectra considered
above and differ only in signals characteristic of alkyl
groups present in the molecule.
Bruker-300 MHz instrument of AVANCE type.
Deuterated water (D2O) and methanol-d4 served as
solvents. The chemical shifts are given in ppm on the δ
scale relative to hexamethyldisiloxane as internal
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 9 2009

1580
GAMZAEVA et al.
Table 2. Antimicrobial properties of the compounds synthesized as additives to M-10 oil
Microorganism suppression zone, cma
mixture of bacteria mixture of fungi in
Compound
no.
Compound
с, %
in BEA
WA
2.5
1.2
3.2
1.6
+
1.0
0.5
1.0
0.5
1.0
+
+
I
N−CH2CH2OH
+
III
N−CH2CH2OCOC6H5
+
3.6
+
NCH2CH2OH
I−
IV
0.5
1.5
+
CH
H3C CH3
2+
1.0
0.5
+
+
2.0
1.0
2Br−
N−CH2CH2 N
IX
XI
C4H9
C4H9
2.4
1.0
0.5
+
+
+
+
2Br−
N−CH2CH2 N
1.2
C5H11
C5H11
1.0
0.5
1.8–2.0
0.9–1.0
1.6–2.0
0.8–1.1
8-Oxyquinoline
M-10 oil without additives
a (+) denotes abundant growth of microorganisms around a well in a Petri dish.
–
+ +
reference. The IR spectra were recorded with a
Specord-75 instrument in liquid films or in mineral oil.
The antimicrobial properties of the compounds were
examined by the well method in an agar medium in
conformity with GOST (State Standard) 9.052–88 and
GOST 9.082–77. Tests were performed with pure
strains of the fungi (Asperigillus niger, Cladosporium
resinae, Penicillium chrosegenum, Chaltonium
globosum) and bacteria (Mycobacterium lacticola,
Pseudomonas aeriginosa), which widely occur in
petroleum products and are their aggressive destruc-
tors. The microorganisms were grown at a temperature
of 28±2°C in a specially mounted thermostat with a
90–100% humidity in the course of 5–7 days. Wort
agar (WA) and beef-extract agar (BEA) served as
nutrition media for fungi and bacteria, respectively.
reaction mixture was heated at the same temperature
on a water bath for 5 h. After that, the reaction product
was cooled and the precipitate was several times
extracted with dry ether. The solvent was evaporated
and the residue was subjected to vacuum distillation.
Yield 9.7 g (75%), bp 64–65°C (1 mm Hg), nD20
1.4712, Rf 0.69.
Found, %
H
Calculated, %
H
C
N
C
N
66.01
11.78 11.01
65.07
11.70
10.84
Formula: C7H15NO
1-(2-Phenylcarbonyloxyethyl)piperidine (III). To
a solution of 6.5 g (0.05 mol) of 1-hydroxy-2-
piperidinoethane I in 30 ml of carbon tetrachloride was
added 2 g (0.05 mol) of sodium hydroxide and the
mixture was vigorously agitated. The reaction course
was monitored by thin-layer chromatography. To
2-Piperidino-1-ethanol (I). To 17 g (0.2 mol) of
piperidine heated to 70°C was slowly added under
agitation 8 g (0.01 mol) of 2-chloro-1-ethanol. The
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 9 2009

A STUDY OF 2-PIPERIDINO-1-ETHANOL AND ITS DERIVATIVES
1581
separate the target product from sodium chloride, the
reaction mixture was treated with distilled water. The
organic layer was dried over calcium chloride. After
the solvent was evaporated, the reaction product was
recrystallized in a 1 : 1 mixture of isopropanol and
hexane. Yield 9 g (78%), mp 200–201°C, Rf 0.67.
1,2-Bispiperidinoethane (VIII). To a mixture of
17 g (0.2 mol) of piperidine, heated to 100°C, was
added 4.9 g (0.05 mol) of 1,2-dichloroethane. The
reaction mixture was heated at the same temperature
on an oil bath for 5 h. After that, the reaction product
was cooled and the precipitate was several times
washed with dry ethyl ether. The solvent was
evaporated and the reaction product was subjected to
vacuum distillation. Yield 8.3 g (85%), mp 100–101°C
(1 mm Hg), nD20 1.4863, Rf 0.63.
Found, %
H
Calculated, %
C
N
C
H
N
72.37
8.39
6.38
72.07
8.21
6.00
Found, %
H
Calculated, %
Formula: C14H19NO2
C
N
C
H
N
Similarly, 2-piperidinoethyl acetate II, whose
physicochemical constants are listed in Table 1, was
synthesized from 2-piperidinoethanol I and acetyl
chloride.
73.53
12.38 14.42
73.41
12.32
14.27
Formula: C14H24N2
CONCLUSIONS
To obtain quaternary salt V by the reaction of 2-
piperidinoethanol I with butyl bromide, a mixture of
1.29 g (0.01 mol) of 1-hydroxy-2-piperidinoethane I
and 1.37 g (0.01 mol) of n-butyl bromide was heated
on a water bath at 80°C for 5 h. White crystals were
precipitated. The reaction product was dissolved in dry
ethyl ether. Yield 1.86 g (70%), mp 190°C, Rf 0.47.
(1) A purposeful synthesis of some 2-pipe-
ridinoethanol derivatives was performed in order to
determine how the structure of these compounds
affects their antimicrobial properties.
(2) A study of the compounds in an M-10 lubricant
oil (0.5–1%) demonstrated that the presence of the
piperidine moiety in molecules of the compounds
imparts to them effective biocide and, in particular,
fungicide properties. The presence of an ester group in
the molecules enhances their biocide activity.
Found, %
H
Calculated, %
C
N
C
H
N
49.59
9.11
5.38
49.62
9.02
5.26
(3) It was shown that quaternary salts of 2-
piperidinoethanol with isopropyl iodide exhibit only
bactericidal properties, and bisquaternary salts of 1,2-
bispiperidinoethane with alkyl bromides, only
fungicidal properties.
Formula: C16H24BrNO
The other quaternary salts IV, VI, and IX–XI were
synthesized similarly. Their physicochemical constants
are listed in Table 1.
2-Piperidinoethyl chloride (VII). A three-necked
flask equipped with a stirrer, dropping funnel, and
thermometer was charged of 12.9 g (0.1 mol) of 2-
piperidinoethanol I in 50 ml of dry benzene and the
solution was vigorously agitated. Then, 12.9 g
(0.01 mol) of thionyl chloride was added dropwise to
the reaction mixture. An exothermic reaction occurred
and the temperature increased to 50–60°C. The
reaction mixture was agitated at this temperature on a
water bath for 5 h and benzene was evaporated. The
reaction product was distilled in a vacuum. Yield 10 g
75%), bp 72–73°C (1 mm Hg), nD20 1.4115, Rf 0.47.
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57.01
9.50
9.51
56.94
9.56
9.49
Formula: C17H14ClN
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 9 2009