2700
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 11, November, 2015
Tcarkova et al.
hydrin (0.3 g, 4.1 mmol), and H2O (3 mL). The salt 1b (1.0 g)
was purified by column chromatography on silica gel, eluent
chloroform—methanol (2 : 1). The yield of product 1b was 0.8 g
(73%) (see Table 2). Found, m/z: 262.2366 [M]+. C14H32NO3.
Calculated: M = 262.2377.
out a phaseꢀtransfer catalyst gave monoethers 4a—c
(70—75%); in the second step, they were treated with thioꢀ
nyl chloride in the presence of pyridine (Scheme 2).
Nꢀ(2ꢀHydroxyethyl)ꢀN,NꢀdimethylꢀNꢀ{2ꢀ[2ꢀ(2ꢀpropyloxyꢀ
ethoxy)ethoxy]ethyl}ammonium chloride (1c) was obtained simiꢀ
larly to compound 1a from amine 2c (0.6 g, 2.7 mmol), ethylene
chlorohydrin (0.2 g, 3.0 mmol), and H2O (3 mL). The salt 1c
(0.8 g) was purified by column chromatography on silica gel,
eluent chloroform—methanol (5 : 1). The yield of product 1c
was 0.7 g (88%) (see Table 2). Found, m/z: 264.2170 [M]+.
C13H30NO4. Calculated: M = 264.2169.
Scheme 2
Nꢀ[2ꢀ(2ꢀHexyloxyethoxy)ethyl]ꢀN,Nꢀdimethylamine (2b).
A mixture of 0.86 g of 38% aqueous solution of Me2NH (0.32 g,
7.1 mmol), 1ꢀ[2ꢀ(2ꢀchloroethoxy)ethoxy]hexane (3b) (2.00 g,
9.6 mmol), and solid NaOH (0.4 g, 10.5 mmol) was heated
in a sealed tube at 110—115 °C for 15 h. Then, the content of
the tube was diluted with benzene (15 mL) and water (10 mL).
The organic layer was separated, washed with water (3×10 mL),
dried with Na2SO4, and concentrated in vacuo. The residue
(1.70 g) was purified by column chromatography on silica gel,
eluent chloroform—methanol (4 : 1). The yield of amine 2b was
1.60 g (77%) (see Table 1). Found, m/z: 218.2107 [M + H]+.
C12H27NO2. Calculated: M = 218.2115.
3, 4
a
b
R
n
1
2
3
nꢀC9H19
nꢀC6H13
nꢀC3H7
c
Reagents and conditions: i. RBr, KOH, dioxane, 100—105 °C,
5—10 h; ii. SOCl2, PhMe, Py, –5 °C→100 °C, 2 h.
Thus, we synthesized a series of ammonium chlorides
with Nꢀωꢀalkoxyethyl and Nꢀ2ꢀhydroxyethyl substituents
by the alkylation of Nꢀ(ωꢀalkoxyethyl)ꢀN,Nꢀdimethylꢀ
amines with ethylene chlorohydrin in the twoꢀphase
system using water as a solvent. The compounds obtained
are of interest as bactericidal agents, as well as for the
study of the structure—activity relationship.
N,NꢀDimethylꢀNꢀ{2ꢀ[2ꢀ(2ꢀpropyloxyethoxy)ethoxy]ethyl}ꢀ
amine (2c) was obtained similarly to amine 2b from 0.86 g of 38%
aqueous solution of Me2NH (0.32 g, 7.1 mmol), 1ꢀ{2ꢀ[2ꢀ(2ꢀ
chloroethoxy)ethoxy]ethoxy}propane (3c) (2.00 g, 9.5 mmol),
and solid NaOH (0.42 g, 10.4 mmol). The product (1.90 g) was
purified by column chromatography on silica gel, eluent chloroꢀ
form—methanol (4 : 1). The yield of amine 2c was 1.80 g (85%)
(see Table 1). Found, m/z: 220.1917 [M + H]+. C11H25NO3.
Calculated: M = 220.1907.
1ꢀ[2ꢀ(2ꢀChloroethoxy)ethoxy]hexane (3b) was obtained acꢀ
cording to the described procedure5 from monoether 4b
(6.8 g,
Experimental
36 mmol), anhydrous pyridine (3.5 mL, 3.4 g, 43 mmol), SOCl2
(3.1 mL, 5.1 g, 43 mmol), and anhydrous toluene (20.0 mL). The
product (6.8 g) was distilled in vacuo to obtain chloride 3b (6.4 g,
84%) with b.p. 126—128 °C (13—14 Torr) (cf. Ref. 8: b.p. 126 °C
1
H and 13C NMR spectra of compounds in CDCl3 were reꢀ
corded on a Bruker Avance III NanoBay spectrometer (300.28 MHz),
using signals of residual protons (δ 7.28) and carbon atoms
(δ 77.20) of the solvent as a internal reference. 2D Correlation
1
3
(14 Torr)). H NMR, δ: 0.84 (t, 3 H, Me, JH,H = 6.9 Hz);
COSY {1H; H}, HSQC, and HMBC{1H; 13C} spectra were reꢀ
1.20—1.39 (m, 6 H, C3H6Me); 1.55 (quint, 2 H, CH2Bu, 3JH,H
=
1
corded using a standard Bruker procedure. High resolution mass
spectra (ESI) were recorded on a Bruker micrOTOF II instruꢀ
ment. Aldrich silica gel (130—270 mesh, 60 Å) was used for
column chromatography. Solvents were purified and dried acꢀ
cording to the known procedures.7 The syntheses of N,Nꢀdiꢀ
methylꢀNꢀ(2ꢀnonyloxyethyl)amine (2a), 1ꢀ(2ꢀchloroethoxy)ꢀ
nonane (3a), and ethylene glycol monononyl ether (4a) were
described earlier.5
= 7.1 Hz); 3.42 (t, 2 H, OCH2C5H11, 3JH,H = 6.8 Hz); 3.53—3.65
3
(m, 6 H, CH2OCH2CH2OC6H13); 3.72 (t, 2 H, ClCH2, JH,H
=
= 5.8 Hz). 13C NMR, δ: 14.18 (Me); 22.77 (CH2Me); 25.92
(CH2Et); 29.75 (CH2Pr); 31.84 (CH2Bu); 42.82 (ClCH2); 70.23
(ClCH2CH2O); 70.88 (CH2OC6H13); 71.54 (CH2CH2OC6H13);
71.75 (OCH2C5H11).
1ꢀ{2ꢀ[2ꢀ(2ꢀChloroethoxy)ethoxy]ethoxy}propane (3c) was
obtained similarly to chloride 3b from monoether 4c (2.3 g,
Nꢀ(2ꢀHydroxyethyl)ꢀN,NꢀdimethylꢀNꢀ(2ꢀnonyloxyethyl)ꢀ
ammonium chloride (1a) was obtained according to the described
12 mmol), anhydrous pyridine (1.2 mL, 1.2 g, 14 mmol), SOCl2
(1.0 mL, 1.6 g, 14 mmol), and anhydrous toluene (8.0 mL). The
product (1.8 g) was purified by column chromatography on silica
gel, eluent chloroform—methanol (49 : 1). The yield of product
3c was 1.6 g (63%). 1H NMR, δ: 0.87 (t, 3 H, Me, 3JH,H = 7.4 Hz);
1.56 (sext, 2 H, CH2Me, 3JH,H = 7.1 Hz); 3.37 (t, 2 H, OCH2CH2Me,
3JH,H = 6.7 Hz); 3.52—3.63 (m, 10 H, CH2OCH2CH2OCH2ꢀ
procedure5 from amine 2a
(1.2 g, 5.6 mmol), ethylene chloroꢀ
hydrin (0.5 g, 6.1 mmol), and H2O (3 mL). The salt 1a (1.5 g)
was purified by column chromatography on silica gel, eluent
chloroform—methanol (2 : 1). The yield of product 1a was 1.1 g
(67%) (see Table 2). Found, m/z: 260.2573 [M]+. C15H34NO2.
Calculated: M = 260.2584.
3
CH2OPr); 3.71 (t, 2 H, ClCH2, JH,H = 5.8 Hz). 13C NMR,
Nꢀ[2ꢀ(2ꢀHexyloxyethoxy)ethyl]ꢀNꢀ(2ꢀhydroxyethyl)ꢀN,Nꢀ
dimethylammonium chloride (1b) was obtained similarly to comꢀ
pound 1a from amine 2b (0.8 g, 3.7 mmol), ethylene chloroꢀ
δ: 10.63 (Me); 22.94 (CH2Me); 42.83 (ClCH2); 70.17 (CH2OPr);
70.75 (OCH2CH2OPr); 70.83 (ClCH2CH2OCH2CH2O); 71.49
(ClCH2CH2O); 73.21 (OCH2Et).