Synthesis and antimicrobial properties of 3-(β-hydroxyethyl)-1,3- oxazolidins

Article abstract of DOI:10.1134/S1070427212010168

The possibility of synthesis of 3-(β-hydroxyethyl)-1,3-oxazolidin and its substituted derivatives at position 2 by the condensation-heterocyclization of diethanolamine with certain aldehydes and ketones was examined. The structure of the compounds was identifi ed by NMR spectroscopy. We investigated antimicrobial properties of the synthesized compounds against microorganisms that affect the lube oil M-11 and found a dependence of the antimicrobial properties on the nature of the substituent at position 2 of oxazolidin heterocycle.

Full text of DOI:10.1134/S1070427212010168

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2012, Vol. 85, No. 1, pp. 81−84. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.M. Farzaliev, M.T. Abbasova, G.E. Gamidova, Ya.M. Kerimova, G.B. Babaeva, L.R. Safarova, 2012, published in Zhurnal
Prikladnoi Khimii, 2012, Vol. 85, No. 1, pp. 85−88.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis and Antimicrobial Properties
of 3-(β-Hydroxyethyl)-1,3-oxazolidins
V. M. Farzaliev, M. T. Abbasova, G. E. Gamidova, Ya. M. Kerimova,
G. B. Babaeva, and L. R. Safarova
Kuliev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
Received August 30, 2010
Abstract—The possibility of synthesis of 3-(β-hydroxyethyl)-1,3-oxazolidin and its substituted derivatives at
position 2 by the condensation-heterocyclization of diethanolamine with certain aldehydes and ketones was
examined. The structure of the compounds was identified by NMR spectroscopy. We investigated antimicrobial
properties of the synthesized compounds against microorganisms that affect the lube oil M-11 and found
a dependence of the antimicrobial properties on the nature of the substituent at position 2 of oxazolidin heterocycle.
DOI: 10.1134/S1070427212010168
It is known that most of the currently used petroleum
products during storage, transportation, and operation
is affected by microorganisms. Microbial processes
occurring lead to a deterioration of physical-chemical,
operational, and hygienic properties of petroleum prod-
ucts, resulting in reduced service life, and materials and
constructions being in contact with petroleum products
are subjected to corrosion [1].
Therefore, synthesis of novel 1,3-diheterocycloalkane
derivatives deserved attention as possible antimicrobial
agent with respect to petroleum products.
In the study we considered diethanolamine condensa-
tion with certain aldehydes and ketones which resulted
in 1,3-oxazolidin derivatives substituted at position 3 by
β-hydroxyl group and at position 2 by alkyl or aryl group.
Formaldehyde (in the form of paraform), benzalde-
hyde, and its F, Cl, OH-substituted derivatives were used
as aldehydes. Methylpropyl- and methylhexylketones
were applied as ketones.
The most efficient way to protect the petroleum
products from microbial destruction is chemical method:
introduction in their composition of special antimicrobial
additives, biocides.
Diethanolamine condensation with aldehydes and
ketones was carried out according to the known technique
[4] at a molar ratio of initials reagents 1 : 1 by heating in
benzene or toluene which was taken according to boiling
point of the initial aldehyde or ketone, with azeotropic
distillation of a reaction water into Dean–Stark trap. The
reaction end was determined by completion of water
release. Physical chemical constants and data of 1H NMR
spectra of the products are listed in the table. In addition,
for clarity we recorded 13C NMR spectra of compounds
II and III.
Since many biologically active compounds contain
structural fragments of N–C–O, N–C–N, and N–C–S,
compounds with these fragments in their structure were
obtained prior to synthesize new substances which are
promising as antimicrobial additives for mineral oils.
Thus, the condensation-heterocyclization of alkanol
amines [2] (or alkylene diamines [3]) was developed
with formaldehyde and hydroxyl-containing compounds
derived from N-alkoxymethyl derivatives of 1,3-dihet-
erocycloalkanes (1,3-oxazines, 1,3-oxazolidins, 1,3-per-
hydropyrimidines, 1,3-imidazolidines). Microbiological
tests have shown high efficiency and broad spectrum of
antimicrobial action of these compounds to the microor-
ganisms which affect petroleum products.
Diethanolamine condensation with formaldehyde
(in the form of paraform) at the 1 : 1 ratio of the initial
reagents proceeds readily. 3-(β-Hydroxyethyl)-1,3-
oxazolidin with 90% yield was obtained after distilling
81

82
FARZALIEV et al.
Physicochemical constants of 3-(β-hydroxyethyl)-1,3-oxazolidin and its derivatives
Content N, %
bp, °С/Р,
mm Hg
Yield,
%
1Н NMR spectrum, chemical shift δ,
Compound
nD20
ppm
found calculated
3-(β-Hydroxyethyl)-1,3-
oxazilidin (I)
85–87/3
90.0
1.4786 12.1
11.96
10.69
4.19 s (2Н, ОСН2N); 3.68 t (2Н,
ОСН2С); 3.55 t (2Н, ССН2О); 2.92 t
(2Н, ССН2N); 2.60 t (NСН2С)
3-(1-Hydroxy-2-oxabutyl- Decomposition Quantita- 1.4720 11.5
4)-1,3-oxazilidin (II)
4.23 s (2Н, ОСН2О); 4.19 s (2Н,
ОСН2N); 3.67 t (2Н, ОСН2С); 3.55 t
(2Н, ССН2О); 2.90 t (2Н, ССН2N); 2.63
t (2Н, NСН2О)
occurs at high
temperature
tive
2-Phenyl-3-
(β-hydroxyethyl)-1,3-
oxazilidin (III)
162–163/1
178–182/1
54.5
1.4436 7.25
1.4464 6.98
6.98
6.63
6.7–7.3 m (5H, С6Н5); 4.7 s (1Н,
ОСНN); 3.6–3.7 t (2Н, ОСН2С); 3.3–
3.5 t (2Н, ССН2О); 2.8 t (2Н, ССН2N);
2.5 t (2Н, NСН2С)
2-p-Fluorophenyl-3-
(β-hydroxyethyl)-1,3-
oxazilidin (IV)
56.9
6.7–7.3 m (4Н, С6Н4F); 4.75 s (1Н,
ОСНN); 3.8–3.9 t (2Н, ОСН2С);
3.3–3.5 t (2Н, ССН2О); 2.7–2.8 t (2Н,
ССН2N); 2.4–2.5 t (2Н, NСН2С)
2-(о-Fluorophenyl)-3-
(β- hydroxyethyl)-1,3-
oxazilidin (V)
136–137/1
155–156/1
54.0
66.1
1.4460 6.63
1.5530 6.52
5.59
6.11
Spectrum is analogous to that of IV
2-(p-Chlorophenyl)-3-
(β- hydroxyethyl)-1,3-
oxazilidin (VI)
6.9–7.05 m (4H, С6Н4Cl); 4.8 s (1Н,
ОСНN); 3.8–3.95 t (2Н, OСН2C);
3.3–3.5 t (2Н, ССН2О); 2.2–2.8 m (4Н,
ССН2N and NСН2С)
2-(о-Chlorophenyl)-3-
(β- hydroxyethyl)-1,3-
oxazilidin (VII)
167–171/1
175–177/1
108/0.4
61.2
60.6
50.0
1.5534 6.47
1.5530 6.74
1.4744 8.6
6.11
6.7
6.9–7.1 m (4Н, С6Н4Сl); 4.8 s (1Н,
ОСНN); 3.7–3.9 t (2Н, ClН2О); 3.3–
3.4 t (2Н, ОСН2С); 2.6–2.7 t (2Н,
NСН2С); 2.3–2.5 t (2Н, ССН2N)
2-(о-Oxyphenyl)-3-
(β-hydroxyethyl)-1,3-
oxazilidin (VIII)
6.7–7.0 m (4Н, С6Н4); 5.9–6.2 br.s
(1Н, С6Н5ОН); 4.9 s (1Н, ОСНN);
3.2–4.0 m (4Н, ССН2ОН, ССН2О);
2.0–3.0 m (4Н, ССН2N)
2-Methyl-2-propyl-3-
(β- hydroxyethyl)-1,3-
oxazilidin (IX)
8.09
3.4–3.6 t (2Н, ССН2О); 3.05–3.15 t
(2Н, ССН2ОН); 2.7–2.8 t (2Н, ССН2N);
2.4–2.53 t (2Н, NСН2С); 1.45–1.53 m
(4Н, ССН2СН2); 1.08 s (3Н, СН3С);
0.85–0.95 t (3Н, СН3СН2)
2-Methyl-2-hexyl-3-
(β-hydroxyethyl)-1,3-
oxazilidin (X)
130/0.5
75.7
1.4656 6.75
6.51
3.4–3.6 t (2Н, ССН2О); 2.6–2.8 t
(2Н, NСН2С); 3.05 t (2Н, ССН2ОН);
2.4–2.5 t (2Н, ССН2N); 1.2–1.5 m
(10Н, СН2СН2СН2СН2СН2); 1.05 s
(3Н, СН3С); 0.85–0.95 t (3Н, СН3СН2)
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 85 No. 1 2012

SYNTHESIS AND ANTIMICROBIAL PROPERTIES
83
off a solvent and distillation of residue under a vacuum:
HO
H NCH2CH2OH + C6H4ХCHO
HO
H NCH2CH2OH + CH2O
O
NCH2CH2OH,
_H2O
O
NCH2CH2OH.
_H2O
C6H4Х
III_VIII
I
In the 13C NMR spectrum of the product I a chemical
shift of the signal of 86.90 ppm corresponds to the carbon
atom at position 2 (that is an evidence of heterocycle for-
mation). If the reaction is carried out at a 2 : 3 molar ratio
of diethanolamine to formaldehyde, then an equimolar
mixture of compounds I and II is formed:
where Х = Н (III), o-F (IV), p-F (V), o-Cl (VI), p-Cl
(VII), o-OH (VIII).
The examinations demonstrated that a yield of con-
densation products was 54–66% regardless of the ratio
of initial reagents and depended on the substituent nature
and position in the benzene ring and grew in an order H <
F < OH < Cl therewith o-F < p-F, o-Cl < p-Cl.
1
In the H NMR spectrum of compounds III–VIII
2 HO
HNCH2CH2OH + 3CH2O
a multiplet of 6.7–7.5 ppm field corresponds to the chemi-
cal shifts of protons of aromatic ring. In these compounds,
similar to compounds I, II, in the field of 2.7–2.8 and
3.3–3.5 ppm the signals of protons of methylene groups
of 1,3-oxazolidin heterocycle are observed at positions
C4 and C5, respectively.
O
NCH2CH2OH
_2H2O
I
+
O
NCH2CH2OCH2OH.
In contrast to the reaction of aldehydes that of ke-
tones proceeds slowly however with 55 and 75.7%
yield of 2-methyl-2-propyl- and 2-methyl-2-hexyl-3-(β-
hydroxyethyl)-1,3-oxazolidin, respectively:
II
The formation of mixture of products I and II was
determined by TLC technique and H NMR spectros-
1
copy. A structure of product II was proved with the aid
of a counter synthesis:
HO
H NCH2CH2OH + CH3COR
O
NCH2CH2OH,
_H2O
O
NCH2CH2OH + CH2O
H3C
R
I
IХ, Х
O
NCH2CH2OCH2OH.
where R = C3H7 (IX), C6H13 (X).
1
In H NMR spectra of products IX, X a triplet in
II
0.85–0.95 ppm field corresponds to terminal methyl
groups of hydrocarbon radicals С3Н7 and С6Н13. Singlet
in the field of 1.08 ppm (1.05 ppm) corresponds to pro-
tons of groups СН3 at С2. Signals in region 2.5–2.8 and
3.5–3.6 ppm corresponds to chemical shifts of protons
at С4 and С5.
In the 13C NMR spectrum of compound II unlike that
of I an additional signal was found at 90.07 ppm cor-
responding to the chemical shift of C atom in OCH2OH
group, while the chemical shifts of other atoms C were
identical with chemical shifts of compound I.
Antimicrobial properties of synthesized compounds
were researched in a lubricating oil M-11 composition
(State Standard: GOST 9.082–77 and 9.052–88). The re-
sulting data show that 3-(β-hydroxyethyl)-1,3-oxazolidin
and its methylol derivative possess high antimicrobial
Diethanolamine condensation with benzaldehyde and
its ortho- and para-F,Cl, ortho-OH-substituted derivatives
resulted in 3-(β-hydroxyethyl)-1,3-oxazolidin derivatives
substituted at position 2 by C6H4X:
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 85 No. 1 2012

84
FARZALIEV et al.
properties. Substitution of hydrogen atom at position 2 of
3-(β-hydroxyethyl)-1,3-oxazolidin by phenyl group im-
pairs its bactericide properties. Depending on the nature
and position of substituent in the benzene ring we found
the following order of lowering the fungicidal properties:
o-F > p-F > o-Cl > p-Cl > OH > H.
with formaldehyde) or its substituted derivatives in
position 2.
(2) The synthesized compounds owing to their
antimicrobial activity at a 0.25–1.0 wt % concentration
protect lubricating oil against microbiological damage.
The high antimicrobial activity of compounds I, II is
presumably due to the fact that in these substances the
bond between positions 1 and 3 of the oxazolidin ring is
readily broken with formation of formaldehyde that leads
to a death of microbial cells.
REFERENCES
1. Il’ichev, V.D., Bocharov, B.V., and Gorlenko, M.V., Eko-
logicheskie osnovy zashchity ot biopovrezhdenii (Protection
against Biodamages in View of Environmetal Safety),
Moscow: Nauka, 1985.
2. Farzaliev, V.M., Abbasova, M.T., Soltanova, Z.K., and
CONCLUSIONS
Ladokhina, N.P., Az. Khim. Zh., 2006, no. 2, pp. 26–30.
(1) We found that the diethanolamine condensation
with certain aldehydes and ketones was accompanied by
heterocyclization of diethanolamine with the formation
of 3-(β-hydroxyethyl)-1,3-oxazolidin (at condensation
3. Farzaliev, V.M., Abbasova, M.T., Babaeva, G.B., and
Soltanova, Z.K., Az. Khim. Zh., 2007, no. 2, pp. 15–17.
4. Hankins, E.M. and Emmons, W.D., Chem. Abstr., 1962,
vol. 57, p. 12495.
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