Synthesis and properties of some aminothiols of phenylethane series

Article abstract of DOI:10.1134/S1070427209070179

Based on styrene, a method of synthesis of 1-phenyl-1,2-epithioethane, the key compound for the synthesis of ethane-1,2-aminothiols, is developed. Antimicrobial activity of the synthesized compounds is investigated

Full text of DOI:10.1134/S1070427209070179

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 7, pp. 1251−1254. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.T. Guseinova, K.I. Aliev, S.S. Sadatova, V.M. Farzaliev, and M.A. Allakhverdiev, 2009, published in Zhurnal Prikladnoi Khimii,
2009, Vol. 82, No. 7, pp. 1155−1158.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis and Properties of Some Aminothiols
of Phenylethane Series
A. T. Guseinova, K. I. Aliev, S. S. Sadatova, V. M. Farzaliev, and M. A. Allakhverdiev
Baku State University, Baku, Azerbaijan
Kuliev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaidzhan, Baku, Azerbaijan
Received May 4, 2008
Abstract—Based on styrene, a method of synthesis of 1-phenyl-1,2-epithioethane, the key compound for the
synthesis of ethane-1,2-aminothiols, is developed. Antimicrobial activity of the synthesized compounds is
investigated
DOI: 10.1134/S1070427209070179
Aminothiols and their derivatives have a wide range
of physiological activity and can be used to create
adrenoblocators, autoimmunomodulators, antiseptics,
and hypoglikemic means [1, 2]. They can serve as key
compounds for the synthesis of various nitrogen- and
sulfur-containing heterocycles with desirable properties.
The interest to aminothiols extents due to their different
functional properties, in particular, physiological
activity which gives rise to their wide application in
pharmaceutical practice as drug. As is known, the drugs
tiphen diprophen are aminothiol esters and are widely
used currently in medical practice [3].
At the second stage, 1-bromo-2-hydroxy-2-
phenylethane (I) under the action of 20% aqueous
solution of sodium hydroxide was subjected to cyclization
and transformed into corresponding oxirane (II):
1-Phenyl-1,2-epithioethane (III) was prepared on the
basis of anionotropic substitution of oxygen atoms in the
molecule of 1-phenyl-1,2-epoxyethane (II) by the sulfur
atom in the reaction with thiocarbamide in the presence
of a catalytic amount of sulfuric acid, with subsequent
neutralization by a solution of sodium carbonate:
Earlier [4−6] has been shown that aminothiols are
effective antimicrobial additives to lubricating oils. In
continuation of our studies in the field of synthesis of
aminothiols and examining the relationship between
their structure and antimicrobial activity, in this
article are investigated the synthesis of 1-phenyl-1,2-
epithioethane and its nucleophilic addition reactions
with various amines. The synthesis was carried out as
follows: at the first stage styrene was transformed into
1-bromo-2-hydroxy-2-phenylethane (I) by the reaction of
hydrobromination with a bromide−bromate solution:
Nucleophilic addition reactions with 1-phenyl-
1,2-epithioethane to various amines were carried out
in sealed ampoule at a ratio of reacting components
thiirane : amine = 1 : 2. It was found that the yield of
target product increases at the use an excess amine, which
in this case plays a role the solvent. Synthesis of 1,2-
1251

1252
GUSEINOVA et al.
Table 1. Physicochemical characteristics of the synthesized 1,2 -aminoethanethiols IV−XVI
20
structure of the compounds is proved with the use of IR
and NMR spectroscopy.
aminoethanethiols IV−XVI carried out as follows:
In the IR spectra of 1-amino-2-phenyl-2-ethanethiols
there are characteristic absorption band at 3340−
3360 cm–1, corresponding to stretching vibrations of
secondary amine NH groups. Stretching vibrations of
SH groups are revealed by a band at 2545−2550 cm–1.
This band has a weak intensity, and not always could
be identified [7, 8]. In addition, all the synthesized 1,2-
aminoethanethiols IV−XVI have absorption bands at
1060−1070 cm–1, relevant to CN bonds. In the areas
of 1420−1440, 1500−1510, 1610−1620 cm–1 are found
the absorption bands characteristic of stretching C=C
vibrations in aromatic ring.
R1 = R2 = C2H5 (IV); X = CH2 (V); X = O (VI); R1 = H,
R2 = C6H5 (VII); R1 = H, R2 = 2-CH3C6H4 (VIII);
R1 = H, R2 = 3-CH3C6H4 (IX); R1 = H, R2 = 4-CH3C6H4
(X); R1 = H, R2 = 2-CH3OC6H4 (XI); R1 = H, R2 = 3-
CH3OC6H4 (XII ); R1 = H, R2 = 4-CH3OC6H4 (XIII);
R1 = H, R2 = 2-ClC6H4 (XIV); R1 = H, R2 = 3-ClC6H4
(XV); R1 = H, R2 = 4-ClC6H4 (XVI).
1
In the H NMR spectrum of 1-(N-diethylamino)-2-
phenyl-2-ethanethiol IV a triplet signal of six protons
of two methyl groups occurs at 1.15 ppm. In the region
of 2.40 ppm there is a multiplet signals of protons in the
CHCH2 fragment. The signal of proton of SH groups
occurs at 2.15 ppm; it was identified on the basis of
changes in the spectrum upon the addition of D2O.
Synthesized 1-amino-2-phenyl-2-ethanethiols (1,2-
aminoethanethiols) IV−XVI are a colorless liquid with
a characteristic odor. If long-term storage the liquid
yellows. Compounds IV−XVI are well soluble in organic
solvents but insoluble in water.
Nonequivalent protons of aromatic rings give a signal
in the form of two triplets, at 6.40 and 6.75 ppm.
Physico-chemical constants of the synthesized
compounds are given in Table. 1.
1
The H NMR spectrum of remaining 1-amino-2-
phenyl-2-ethanethiols V−XVI are similar to the spectrum
of compounds IV, but differs by the position the signals
of respective substituents (pentamethylenimino-,
morpholino-, various substituted phenyl radicals, etc.).
Purity of the synthesized 1-amino-2-phenyl-2-
ethanethiols IV−XVI is confirmed by data of elemental
analysis, thin layer and gas-liquid chromatography; the
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 7 2009

SYNTHESIS AND PROPERTIES OF SOME AMINOTHIOLS
1253
Table 2. Antimicrobial activity of 1,2-aminoethanthiols
IV−XI in oil M-11
The synthesized compounds were tested in accordance
with GOST 9.052-75 and 9.085-75 as antimicrobial
additives for lubricating oil M-11. For the examination
are used bacteria Prendomanas aeruginosa and fungi
Aspergillus-niger and Canadida-tragicalic.
The results of testing the synthesized compounds
as antimicrobial additives to oil M-11 are shown in
Table 2. The oil M-11 does is not biologically stable and
is destructed by these organisms.
beef-extract gar
The synthesized compounds have a pronounced
antimicrobial action at low concentrations (0.5−1.0%),
well soluble in the oil M-11 and do not stimulate
corrosion. The synthesized 1,2-aminoethanethiols
IV−XVI are more effective than industrial antimicrobial
additive 2-mercaptobenzthiazol taken as a reference.
As can be seen from the Table 2, at adding 0.5−1.0%
of 1-diethylamino-2-phenyl-2-ethanethiol IV the width of
the zone for bacteria is 0.5−1.2, and for the fungi 0.8−1.5.
Similar picture is observed at the testing the antimicrobial
effectiveness of 1-(N-phenylamino)-2-phenyl-2-
ethanethiol VII, where the width of the zone of inhibition
by bacteria is 0.9−1.9, by fungi 1.2−2.3 cm. In the case
of 2-mercaptobenzthiazol at concentrations 0.5−1.0%
the area of oppression by bacteria is 0.4−1.0, and by
fungi, 0.8−1.5 Other synthesized 1-amino-2-phenyl-
2-ethanethiols V−XVI also exhibit high antimicrobial
activity, and their effect on fungi is much stronger than
on the bacterial culture.
As can be seen from Table 2, 1,2-aminoethanethiols
V and VI containing heterocyclic amine fragments
have a lower antimicrobial activity compared to 1,2-
aminoethanethiols with aryl-substituted fragments.
Methyl and methoxy substituents in arylamine fragments
of 1,2-aminoethanethiols do not significantly affect their
antimicrobial activity. However, in going from the methyl
and methoxy substituents to chlorine the antimicrobial
activity increases significantly. Thus, as a result of the
research is found the relationship between the structure
of the synthesized compounds and their antimicrobial
activity.
TLC (Silufol, eluent hexane−isopropyl alcohol 1 : 3,
development in iodine vapor).
Bromide−bromate solution is prepared as follows. In
the flask of 3 liter was poured 1.25 l of distilled water and
dissolved 125 g of KBr. Then, with stirring was added
dropwise 40 ml of bromine and stirring was continued
till complete bromine dissolving.
EXPERIMENTAL
1-Bromo-2-hydroxy-2-phenylethane (I). A three-
neck 2 l flask equipped with two dropping funnel, one
of which is 100 ml, and the other 1000 ml (for the
bromide−bromate solution), was placed in a water bath.
The temperature in the bath was maintained at 90−100°C.
The reaction was carried out by adding alternately
The IR spectra were registered on a Specord 75-IR
instrument, the 1H NMR spectra on a VXR-400S device
(400 MHz) for the solutions of substances in DMSO-
d6, internal reference TMS. Purity raw materials and
the analysis of reaction products were carried out by
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 7 2009

1254
GUSEINOVA et al.
was obtained, bp 118−120°C (0.1 mm Hg), nD20 1.5555,
Rf 0.51. Found, %: C 73.07, H 6.86, N 6.43, S 13.76.
C14N15NS. Calculated (%): C 73.32, H 6.59, N 6.11,
S 13.97.
portions 52 g (0.5 mol) of styrene, followed by bromide-
bromate solution. Initially was added 250 ml of distilled
water, then was poured 10−15 g styrene, followed by
50 ml of bromide-bromate solution. The next portion
of styrene was added after the solution bleaching. The
reaction was carried out for 3 h. Then the reaction mixture
was stired for 30 min at 90−100°C. Then the bottom layer
(containing organic bromide) was separated from the
water, dried over sodium sulfate and subjected to vacuum
distillation. 19 g (20%) of compound I was obtained, bp
114°C (4 mm Hg), nD20 1.5782.
Similarly have been synthesized other 1-amino-2-
phenyl-2-ethanethiols IV−XVI.
CONCLUSIONS
(1) The method of synthesis of 1-phenyl-1,2-epithio-
ethane on the basis of styrene is developed.
1-Phenyl-1,2-epoxyethane (II). To a mixture of
20.1 g (0.1 mol) of 1-bromo-2-hydroxy-2-phenylethane
I and 50 ml of hexane at vigorous stirring was added
dropwise g 20% solution of sodium hydroxide. Then the
flask content was heated at 60°C for 2 h, the reaction
mixture was then cooled, washed several times with
water to neutral reaction and dried over anhydrous
sodium sulfate.After distilling the solvent off, the reaction
products were distilled with a 20-cm Vigre column.
Compound II of 9 g (80%) was obtained, nD20 1.5368
(published [9] nD20 1.5342).
(2) 1-Amino-2-phenyl-2-ethanethiols, synthesized in
the interaction of 1-phenyl-1,2-epithioethane with various
amines, have antimicrobial activity.
(3)Arelationship between the structure of aminothiols
and their antimicrobial activity is revealed.
REFERENCES
1. Magerramov, A.M., Allakhverdiev, M.A., Guseino-
va, A.T., and Kuliev, D.A. Aminotioly i ikh proizvodnye
(Aminothiols and Their Derivatives), Baku: Bakin. Gos.
Univ., 2007.
1-Phenyl-1,2-epithioethane (III). To the three-neck
flask was placed 7.6 g (0.1 mol) of thiourea and 3 ml
of sulfuric acid (1 eq. of acid in 350 ml of water). At
vigorous stirring the reaction mixture was cooled to
5−10°C and at that temperature was added dropwise
11 g (0.1 mol) of 1-phenyl-1,2-epoxyethane II. The
mixture was maintained at room temperature for 1 h, and
then was hydrolyzed with 10.6 g (0.1 mol) of sodium
carbonate dissolved in 45 ml of water. The water layer
was separated and extracted with ether (40 ml). The
extract was combined with the organic layer and dried
over anhydrous sodium sulfate. After distilling ether off,
the residue was distilled in a vacuum. 11 g (87%) of
1-phenyl-1 ,2-epitioethane III was obtained, bp 87−88°C
(4 mm Hg), nD20 1.6030 (published [10] bp 30°C at 0.01 mm
Hg, nD20 1.6015).
2. Magerramov, A.M. and Allakhverdiev, M.A., Bifunk-
tsional’nye aminnye soedineniya (Bifunctional Amine
Compounds), Baku: “Chashyoglu”, 2005.
3. Rubtsov, M.V. and Baichikov, A.T., Sinteticheskie
khimikofarmatsevticheskie preparaty (Synthetic Chemical
Farmaceutic Chemicals), Moscow: Meditsina, 1971.
4. Guseinova, A.T., Magerramov, A.M., Nadim, Kh.A., and
Allakhverdiev, M.A., Zh. Prikl. Khim., 2002, vol. 75, no, 8,
pp.1306−1308.
5. Allakhverdiev, M.A., Farzaliev, V.M., Guseino-
va, T.M. et al., Zh. Prikl. Khim., 1994, vol. 67, no. 11,
pp. 1872−1876.
6. Allakhverdiev, M.A., Farzaliev, V.M., and Guseino-
va, T.M., Zh. Org. Khim., 1995, vol. 31, no. 1, pp. 532−534.
7. Atavin, A.S., Shostakovskii, M.F., Vyalykh, E.T., and
Trofimov, B.A., Zh. Org. Khim., 1970, vol. 6, no. 2,
pp. 222−227.
1-(N-Phenylamino)-2-phenyl-2-ethanethiol (VII).
Amixture of 9.3 g (0.1 mol) of aniline and 6.8 g (0.05 mol)
of 1-phenyl-1,2-epithioethane III was heated in a sealed
ampoule at a boiling water bath for 8 h. After cooling
the ampoule was open and the reaction mixture was
distilled under reduced pressure. First was distilled the
excess of aniline, and then the target product of reaction.
7.9 g of 1-(N-phenylamino)-2-phenyl-2-ethanethiol VII
8. Bellamy, L.J., The Infra-red Spectra of Complex Molecules,
London: Methuen, 1958.
9. Malinovskii, M.S., Okisi olefinov i ikh proizvodnykh (Olefin
Oxides and Their Derivatives), Moscow: Goskhimizdat,
1961.
10. Stewart, J.M., J. Org. Chem., 1963, vol. 29, p.1655.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 7 2009