Synthesis of dialkylaminomethoxy derivatives of 3-aryloxy-1-(ethylsulfanyl) propanes

Full text of DOI:10.1134/S1070428010020090

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 198−201. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.G. Mamedbeili, I.A. Dzhafarov, K.A. Kochetkov, T.G. Kyazimova, N.D. Kagramanov, 2009, published in Zhurnal
Organicheskoi Khimii, 2010, Vol. 46, No. 2, pp. 205−208.
Synthesis of Dialkylaminomethoxy Derivatives
of 3-Aryloxy-1-(ethylsulfanyl)propanes
E. G. Mamedbeilib, I.A. Dzhafarova, K. A. Kochetkovc,
T. G. Kyazimovab, and N. D. Kagramanovc
aAzerbaijanPedagogical University, Baku, Azerbaijan
bInstitute of Petrochemical Processes, Azerbaijan National Academy of Sciences, Baku, AZ1025Azerbaijan
e-mail: eldar_mamedb yli@mail.ru
cNesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow
Received January 14, 2009
DOI: 10.1134/S1070428010020090
Organic compounds containing sulfur and nitrogen are
widely used as antioxidant, anticorrosion, and anti-
microbial additives to fuels and lubricants [1]. They are
also biologically active compounds and are involved into
the composition of pharmaceuticals [2]. The preparation
of new series of compounds proceeding from accessible
raw materials and refinement of the general synthetic
procedures is highly urgent [3].
Further by Mannich condensation of alcohols IIIa and
IIIb with formaldehyde and secondary amines IVa–
IVe we obtained new representatives of dialkylamino-
methoxy-3-aryloxy(ethylsulfanyl)propanes Va–Vj
(Scheme 2).
The synthesis of amino derivatives Va–Vj was
performed at 45–50°C over 4–5 h at equimolar amounts
of the components. The yield of compounds Va–Ve from
alcohol IIIa was 70–78%, of compounds Vf–Vj from
alcohol IIIb attained 70–75%, the yield of N,N-dibutyl-
amino derivatives Vb and Vg was somewhat higher (78
and 76% respectively).
We reporet here on the results of syntheses and study
of the properties of new dialkylaminomethoxy derivatives
of 3-aryloxy-1-(ethylsulfanyl)propanes. To this end we
first synthesized previously unknown sulfur-containing
aryloxy alcohols IIIa and IIIb by reaction of phenols Ia
and Ib with 1-chloro-3-(ethyl-sulfanyl)propan-2-ol (II)
in alkaline medium (Scheme 1). The synthesis of alcohols
IIIa and IIIb was carried out at equimolar ratio of initial
compounds in alkaline medium (40% aqueous NaOH) at
70–75°C over 4–5 h, the yield of the alcohols was 70–
72%.
The synthesized alcohols IIIa and IIIb and their amino
derivatives Va–Vj are transparent foxy liquids. They are
insoluble in water but well soluble in organic solvents
(ethanol, acetone, benzene, CCl4 etc.).
Scheme 2.
Scheme 1.
IIIа, IIIb + CH2O + HNR2
IVа_IVe
+
OH
R
Cl
SEt
OH
EtS
O
R
Iа, Ib
_H2O
II
O
NR2
Vа_Vj
NaOH
_H2O, _NaCl
R
O
SEt
OH
IIIа, IIIb
R = H (Va–Ve), Me (Vf–Vj); NR2 = NEt2 (IVa, Va, Vf),
NBu2 (IVb, Vb, Vg), piperidino (IVc, Vc, Vh), morpholino
(IVd, Vd, Vi), N(CH2)6 (IVe, Ve, Vj).
R = H (a), Me (b).
198

SYNTHESIS OF DIALKYLAMINOMETHOXY DERIVATIVES
199
The composition and structure of compounds obtained
were established from the elemental analysis, IR, 1H NMR,
and mass spectra. The purity of compounds was checked
by GLC. The IR spectra of compounds IIIa and IIIb
contained broad absorption bands in the region 3350–
3300 cm–1 characteristic of hydroxy group which were
lacking in the spectra of compounds Va–Vj. In the IR
spectra of compounds Va–Vj absorption bands were
present in the 1220–1010 cm–1 characteristic of the C–N
bond [4], and also in the region 2910–2895 and 2830–
2820 cm–1 characteristic of vibrations of the C–H bond
in the groups CH3 and CH2 respectively. 1H NMR spectra
of compounds synthesized have a typical pattern and also
confirm the assigned structure. In the mass spectra
(electron impact) of compounds IIIa and IIIb, Va–Vj
the peaks were observed of the corresponding molecular
ions and of their fragmentation products.
distilled in a vacuum. Yield 32.2 g (72%), bp 146–147°C
(1 mm Hg), n240 1.5508, d420 1.1126. MRD 60.86, calc.
60.87. IR spectrum, ν, cm–1: 3350 (OH), 2920 (CH3),
1
2880 (CH2). H NMR spectrum, δ, ppm: 1.36 t (3H,
SCH2CH3), 2.1 s (OH), 2.5 t (2H, SCH2), 2.75 d.d (2H,
SCH2CH), 3.7 m (OCH), 7.0 m (3H, n-, m-C6H5), 7.34
m (2H, o-C6H5). Mass spectrum, m/z (Irel, %): 212 (10)
[M]+, 195 (100), 147 (20), 47 (25). Found, %: C 62.04;
H 7.45; S 14.92. C11H16O2S. Calculated, %: C 62.20;
H 7.54; S 15.07. M 212.31.
3-(p-Tolyloxy)-1-(ethylsulfanyl)propan-2-ol (IIIb)
was analogously obtained from 27.02 g (0.25 mol) of
p-cresol (Ib) and 38.67 g (0.25 mol) of alcohol II. Yield
47.5 g (70%), bp 150–152°C (1 mm Hg), n240 1.5448, d420
1.0898. MRD 65.64, calc. 65.51. IR spectrum, ν, cm–1:
3200 (OH), 2920 (CH3), 2870 (CH2). 1H NMR spectrum,
δ, ppm: 1.34 t (3H, SCH2CH3), 2.35 s (3H, n-CH3), 2.5 t
(2H, SCH2), 2.7 m (OH), 2.75 d.d (2H, SCH2CH), 3.6 m
(OCH), 6.85–7.10 m (4H, C6H4). Mass spectrum, m/z
(Irel, %): 226 (10) [M]+, 209 (100), 105 (100), 59 (20).
Found; %: C 63.53; H 7.92; S 14.02. C12H18O2S.
Calculated, %: C 63.68; H 8.01; S 14.16. M 226.32.
The obtained 3-(4-methylphenoxy)-1-(ethylsulfanyl)-
propanes Va–Vj were tested as antimicrobial agents in
the medicine. They demonstrated a more pronounced
antimicrobial activity than the preparations commonly
used in the medicine (ethanol, phenol, acrinol, and nitro-
fungin). Thus they can be suggested for application as
new efficient antimicrobial agents.
Dialkylaminomethoxy derivatives of aryloxy-sub-
stituted ethylsulfanylpropanes Va–Vj. To a solution
of 0.02 mol of alcohol IIIa or IIIb and 0.02 mol of
formaldehyde (which obtained from paraformaldehyde
in the course of the reaction) in 30 ml of anhydrous
benzene at 20–22°C was added dropwise while stirring
0.02 mol of freshly distilled amine IVa–IVe. The stirring
was continued for 1 h at the same temperature, then 1–
3 h at 40–50°C. On removing the solvent the residue
was distilled in a vacuum.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
1
UR-20 in the region 4000–400 cm–1. H NMR spectra
were registered on a spectrometer Bruker WP-400
(400 MHz), solvent CDCl3, chemical shifts reported with
respect to TMS. Mass spectra were obtained on
an instrument VG-7070E (ionizing electrons energy
70eV). The chromatography analysis of the reaction
mixtures and testing the purity of compounds synthesized
was performed on a chromatograph LKhM-8MD {steel
2-(N,N-Diethylaminomethoxy)-3-phenoxy-1-
(ethylsulfanyl)propane (Va) was obtained from 4.25 g
of compound IIIa, 0.6 g of paraform, and 1.46 g of
diethylamine. Yield 4.3 g (72%), bp 158–160°C (1 mm
Hg), n240 1.5155, d240 1.0213. MRD 87.90, calc. 88.13. IR
spectrum, ν, cm–1: 2920 (CH3), 2880 (CH2), 1225 (C–
N). 1H NMR spectrum, δ, ppm: 1.36 t (3H, SCH2CH3),
1.62 t (6H, 2NCH2CH3), 2.65–2.25 m (10H, OCH2,
2NCH2, 2SCH2), 3.4 m (OCH), 4.2 d.d (2H, OCH2N),
7.1 m (3H, n-, m-C6H5), 7.34 m (2H, o-C6H5). Found,
%: C 64.46; H 9.04; N 4.63; S 10.66. C16H27NO2S.
Calculated, %: C 64.61; H 9.15; N 4.71; S 10.78.
column (3000 × 3 mm), stationary phase 5% poly(ethylene
glycol) succinate on dinochrome P], carrier gas helium
(40 cm3/min), detector cataharometer, oven temperature
150°C, vaporizer temperature 240°C.
3-Phenoxy-1-(ethylsulfanyl)propan-2-ol (IIIa). To
a mixture of 23.53 g (0.25 mol) of phenol and 10 g of
NaOH in 15 ml of water at 70–75°C under vigorous
stirring was added dropwise 38.67 g (0.25 mol) of alcohol
II. The stirring was continued for 3–4 h. After cooling
benzene was added to the mixture, the organic layer was
washed with water to neutral washings, and dried with
MgSO4. On distilling off the solvent the residue was
2-(N,N-Dibutylaminomethoxy)-3-phenoxy-1-
(ethylsulfanyl)propane (Vb) was obtained from 4.25 g
(0.02 mol) of compound IIIa, 0.6 g of paraformaldehyde,
and 2.58 g (0.02 mol) of dibutylamine (IVb).Yield 5.52 g
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MAMEDBEILI et al.
200
(78%), bp 184–186°C (1 mm Hg), n240 1.5010, d420 1.0976.
MRD 110.89, calc. 111.37. IR spectrum, ν, cm–1: 2920
(CH3), 2890 (CH2), 1500 (C–Carom), 1200 (C–N). 1H NMR
spectrum, δ, ppm: 0.95 m (6H, 2CH3), 1.34 m (3H,
SCH2CH3), 1.55–1.65 m (8H, 4CH2), 2.55–2.70 m (10H,
OCH2, 2NCH2, 2SCH2), 3.4 m (OCH), 4.20 d.d (2H,
OCH2N), 7.0 m (3H, n-, m-C6H5), 7.35 m (2H, o-C6H5).
Mass spectrum, m/z (Irel, %): 353 [M]+ (15), 282 (5), 147
(45), 119 (100), 98 (60), 75 (70). Found, %: C 67.78;
H 9.89; N 3.88; S 8.95; C20H35NO2S. Calculated, %:
C 67.94; H 9.98; N 3.96; S 9.07. M 353.53.
[M – C9H20NO]+, 119 (72) [M – C10H23OS]+, 75 (100).
Found, %: C 66.71; H 8.96; N 4.25; S 9.82. C18H29NO2S.
Calculated, %: C 66.83; H 9.04; N 4.33; S 9.91. M 323.19.
2-(N,N-Diethylaminomethoxy)-3-(p-tolyloxy)-1-
(ethylsulfanyl)propane (Vf) was obtained from 4.25 g
of compound IIIb, 0.6 g of paraformaldehyde, and 1.46 g
of diethylamine (IVa). Yield 4.36 g (70%), bp 164–165°C
(1 mm Hg), n240 1.5150, d420 1.0148. MRD 92.55, calc.
92.78. IR spectrum, ν, cm–1: 2910 (CH3), 2890 (CH2),
1
1215 (C–N). H NMR spectrum, δ, ppm: 0.95 t (6H,
2CH3), 1.36 t (3H, SCH2CH3), 2.35 s (3H, p-CH3), 2.60–
2.80 m (10H, 2NCH2, OCH2, 2SCH2), 3.25 m (OCH),
4.20 d.d (2H, OCH2N), 6.85–7.10 m (4H, C6H4). Mass
spectrum, m/z (Irel, %): 311 (10) [M]+, 239 (15), 147 (45)
119 (100), 101 (45), 75 (60), 47 (30). Found, %: C 65.41;
H 9.30; N 4.42; S 10.19. C17H29NO2S. Calculated, %:
C 65.55; H 9.38; N 4.49; S 10.29. M 311.19.
2-Piperidinomethoxy-3-phenoxy-1-(ethylsulfan-
yl)propane (Vc) was obtained from 4.25 g of compound
IIIa, 0.6 g of paraformaldehyde, and 1.72 g of piperidine
(IVc). Yield 4.46 g (72%), bp 173–175°C (1 mm Hg),
n240 1.5312, d420 1.0568. IR spectrum, ν, cm–1: 2920 (CH3),
2820 (CH2), 1020 (C–N), 720 (C–S). 1H NMR spectrum,
δ, ppm: 1.35 t (3H, ½CH2CH3), 1.65 t (6H, 3CH2cycle),
2.60–2.90 m (6H, OCH2, 2½CH2), 3.3 m (OCH), 4.20 d.d
(2H, OCH2N), 7.0 m (3H, p-, m-C6H5) 7.34 m (2H,
o-C6H5). Mass spectrum, m/z (Irel, %): 309 (20) [M]+,
235 (10), 147 (50), 119 (100), 75 (70), 47 (27). Found, %:
C 65.89; H 8.76; N 4.46; S 10.26. C17H27NO2S.
Calculated, %: C 66.98; H 8.79; N 4.53; S 10.36. M 309.44.
2-(N,N-Dibutylaminomethoxy)-3-(p-tolyloxy)-1-
(ethylsulfanyl)propane (Vg) was obtained from 4.52 g
of compound IIIb, 0.6 g of paraformaldehyde, and 2.58 g
of dibutylamine (IVb). Yield 5.59 g (76%), bp 208–209°C
(1 mm Hg), n240 1.5038, d420 0.9812. MRD 110.89, calc.
111.37. IR spectrum, ν, cm–1: 2920 (CH3), 2890 (CH2),
1
1020 (C–N). H NMR spectrum, δ, ppm: 0.95 m (6H,
2-Morpholinomethoxy-3-phenoxy-1-(ethyl-
sulfanyl)propane (Vd) was obtained from 4.25 g of com-
pound IIIa, 0.6 g of paraformaldehyde, and 1.74 g of
morpholine (IVd). Yield 4.79 g (74%), bp 173–175°C (1
mm Hg), n240 1.5366, d420 1.1066. MRD 87.84, calc. 87.98.
IR spectrum, ν, cm–1: 2900 (CH3), 2860 (CH2), 1200 (C–
N), 730 (C–S). 1H NMR spectrum, δ, ppm: 1.35 t (3H,
½CH2CH3), 2.6–2.8 m (14H, 3OCH2, 2NCH2, 2SCH2),
3.20 t (OCH), 4.2 d.d (2H, OCH2N), 7.0 m (3H, p-, m-
C6H5), 7.34 m (2H, o-C6H5). Found, %: C 61.52; H 8.01;
N 4.43; S 10.20. C16H25NO3S. Calculated, %: C 61.70;
H 8.09; N 4.50; S 10.30.
2CH3), 1.35 t (3H, SCH2CH3), 1.35–1.65 m (8H, 4CH2),
2.35 sC (3H, p-CH3), 2.60–2.80 m (10H, 2NCH2,
2SCH2, OCH2), 3.2 m (OCH), 4.22 d.d (2H, OCH2N),
6.85–7.10 m (4H, C6H4). Mass spectrum, m/z (Irel, %):
367 (19) [M]+, 306 (5), 119 (100). Found, %: C 71.59;
H 10.52; N 3.77; S 8.67. C21H37NO2S. Calculated, %:
C 71.74; H 10.60; N 3.81; S 8.72. M 367.56.
2-Piperidinomethyleneoxy-3-(p-tolyloxy)-1-
(ethylsulfanyl)propane (Vh) was obtained from 4.52 g
of compound IIIb, 0.6 g of paraformaldehyde, and 1.74 g
of piperidine. Yield 4.62 g (71%), bp 191–193°C (1 mm
Hg), n240 1.5296, d240 1.0459. MRD 95.48, calc. 95.37. IR
spectrum, ν, cm–1: 2920 (CH3), 2830 (CH2), 1020 (C–
N). 1H NMR spectrum, δ, ppm: 0.95–1.18 (6H, 3CH2cycle),
1.36 t (3H, SCH2CH3), 2.35 s (3H, p-CH3), 2.60–2.90 m
(10H, OCH2, NCH2, SCH2), 3.24 quintet (OCH),
4.20 d.d (2H, OCH2N), 6.95–7.21 m (4H, C6H4). Mass
spectrum, m/z (Irel, %): 323 (10) [M]+, 262 (5), 208 (15),
147 (40), 119 (100), 98 (55), 75 (70), 47 (30). Found, %:
C 66.70; H 8.96; N 4.27; S 9.81. C18H29NO2S.
Calculated, %: C 66.83; H 9.03; N 4.32; S 9.91. M 323.19.
2-Hexamethyleneiminomethoxy-3-phenoxy-1-
(ethylsulfanyl)propane (Ve) was obtained from 4.25 g
of compound IIIa, 0.6 g of paraformaldehyde, and 1.98 g
hexamethyleneimine (IVe). Yield 4.72 g (73%), bp 182–
184°C (1 mm Hg), n420 1.5308, d420 1.0526. MRD 95.05,
calc. 95.37. IR spectrum, ν, cm–1: 2920 (CH3), 2850
1
(CH2), 1200 (C–N), 730 (C–S). H NMR spectrum, δ,
ppm: 1.35 t (3H, SCH2CH3), 1.65 t (8H, CH2cycle), 2.6–
2.9 m (10H, OCH2, 2NCH2, 2SCH2), 3.25 t (OCH),
4.20 d.d (2H, OCH2N), 7.0 m (3H, p-, m-C6H5), 7.34 m
(2H, o-C6H5). Mass spectrum, m/z (Irel, %): 323 (10),
225 (6) [M – C6H12N]+, 194 (17) [C11H23OS]+, 133 (36)
2-Morpholinomethoxy-3-(p-tolyloxy)-1-(ethyl-
sulfanyl)propane (Vi) was obtained from 4.52 g of
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SYNTHESIS OF DIALKYLAMINOMETHOXY DERIVATIVES
201
compound IIIb, 0.6 g of paraformaldehyde, and 1.74 g
of morpholine. Yield 4.88 g (75%), bp 193–195°C
(1 mm Hg), n240 1.5314, d420 1.0891. MRD 92.52, calc.
92.48. IR spectrum, ν, cm–1: 2900 (CH3), 2840 (CH2),
%: C 66.59; H 9.18; N 4.09; S 9.42. C19H31NO2S.
Calculated, %: C 67.61; H 9.26; N 4.15; S 9.50.
REFERENCES
1
1200 (C–N). H NMR spectrum, δ, ppm: 1.34 t (3H,
1. Kuliev, A.M., Khimiya i tekhnologiya prisadok k maslam
i toplivam (Chemistry and Technology of Oil Additives),
Moscow: Khimiya, 1972.
2. Beletskaya, I.P. andAnanikov, V.P., Eur. J. Org. Chem., 2007,
p. 3431; Beletskaya, I.P. and Cheprakov,A.V., Coord. Chem.
Rev., 2002, vol. 102, p. 1359; Ley, S.V. and Thomas, A.W.,
Angew. Chem., Int. Ed., 2003, vol. 42, p. 5400; Markova, I.V.,
Mikhailov, I.B., and Nezhentsev, M.V., Farmakologiya
(Pharmacology), St. Petersburg: Foliant, 2001.
3. Fernandez-Rodriguez, M.A., Shen, Q., and Hartwig, J.F., J.
Am. Chem. Soc., 2006, vol. 128, p. 2180; Zhu, D., Xu, L., Wu,
F., and Wan. B., Tetrahedron Lett., 2006, vol. 47, p. 5781;
Rout, L., Sen, T.K., and Punniyamurthy, T., Angew. Chem.,
Int. Ed., 2007, vol. 37, p. 2046.
SCH2CH3), 2.35 s (3H, n-CH3), 2.60–2.80 m (14H,
NCH2, 3OCH2, 2SCH2), 3.2 quintet (OCH), 4.20 d.d (2H,
OCH2N), 6.95–7.20(4H, C6H4). Mass spectrum, m/z (Irel,
%): 325 (10) [M]+, 264 (15), 119 (100), 47 (25). Found,
%: C 62.62; H 8.28; N 4.25; S 9.76. C17H27NO3S.
Calculated, %: C 62.74; H 8.36; N 4.30; S 9.85. M 325.17.
2-Hexamethyleneiminomethoxy-3-(p-tolyloxy)-1-
(ethylsulfanyl)propane (Vj) was obtained from 4.5 g of
alcohol IIIb, 0.6 g of paraformaldehyde, and 1.98 g of
hexa-methyleneimine (IVe).Yield 4.93 g (73%), bp 193–
195°C (1 mm Hg), n420 1.5300, d420 1.0455. MRD 99.73,
calc. 100.02. IR spectrum, ν, cm–1: 2920 (CH3), 2840
(CH2), 1060 (CN). 1H NMR spectrum, δ, ppm: 1.35 (3H,
SCH2CH3), 1.65 m (8H, 4CH2cycle), 2.35 s (3H, p-CH3),
2.6–2.9 m (10H, 2NCH2, OCH2, 2SCH2), 3.34 t (OCH),
4.20 d.d (2H, OCH2N), 6.85–7.10 m (4H, C6H4). Found,
4. Gordon, A.J. and Ford, R.A., The Chemist’s Companion,
NewYork: Wiley, 1972.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010