Quaternary ammonium compounds
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 11, November, 2014 2453
amine (12.7 mL, 93.9 mmol), dodecyl bromide (11.7 g, 46.9 mmol),
a 50% aqueous solution of NaOH (2.0 g, 51.6 mmol), and 10 mL
of benzene (see Tables 1 and 2).
Cl, 9.33; N, 3.68. C21H45NO2•HCl. Found (%): C, 66.54;
H, 12.33; Cl, 8.63; N, 3.65.
Synthesis of quaternary ammonium compounds 1a—g, 2a—c,
and 5a—c. Alkylation of tertiary amines 6a,c—h in water (general
procedure). A mixture of amine 6a,c—h (6 mmol) and alkyl
chloride (6 mmol) in water (2—3 mL) was stirred at 60—95 С
for 0.3—4 h and then evaporated in vacuo. The residue was purified
by column chromatography on silica gel in a CHCl3—MeOH (10 : 1)
system or by recrystallization. The reaction conditions in each
particular case, yields, and physicochemical parameters of quaterꢀ
nary ammonium compounds 1a—g, 2a—c, and 5a—c are presented
in Table 3. The data of the 1Н NMR spectra are given in Table 5.
NꢀAlkylꢀNꢀbutylꢀNꢀ(2ꢀhydroxyethyl)ꢀNꢀmethylammonium
(2d—f) chlorides (general procedure). A mixture of amine 6f—h
(5 mmol) and ethylene chlorohydrin (15 mmol) was stirred
at 130—135 С for 3 h and then evaporated in vacuo. The resiꢀ
due was purified by column chromatography on silica gel in
a CHCl3—MeOH (10 : 1) system or by recrystallization (see
Tables 3—4). The yields in each particular case and physicoꢀ
chemical parameters of quaternary ammonium compounds 2d—f
are presented in Table 3. The data of the 1Н NMR spectra are
given in Table 5.
NꢀBenzylꢀN,Nꢀdimethylamine (6b). Benzyl chloride (18.7 g,
148 mmol) was added dropwise with stirring to a 38% aqueous
solution of dimethylamine (40.0 mL, 296 mmol) at 20—25 С,
and then a 30% aqueous solution of NaOH (6.5 g, 163 mmol)
was added. After stirring for 5 h at 20—25 С, the mixture was
diluted with benzene (40 mL). The organic layer was separated
and extracted with dilute HCl (1 : 2, 4×15 mL). A 40% aqueous
solution of NaOH was added to the combined extract to pH 9
(universal indicator paper), and the formed oil was extracted
with benzene (2×30 mL). The extract was dried with Na2SO4,
the solvent was distilled off at atmospheric pressure, and the
residue was distilled (see Tables 1 and 2).
Tertiary amine hydrochlorides (general procedure). Concenꢀ
trated HCl (1 mL) was added dropwise with stirring to a solution
of tertiary amine 6e,g,h (3.5 mmol) in ethanol (5 mL) at
20—25 С. After stirring for 10 min at 20—25 С, the mixꢀ
ture was evaporated in vacuo. The residue was purified by
column chromatography on silica gel in a CHCl3—MeOH
(10 : 1) system.
Nꢀ[2ꢀ(2ꢀDodecyloxyethoxy)ethyl]ꢀN,Nꢀdimethylamine (6e)
was characterized as its hydrochloride obtained using the general
procedure in 97% yield, m.p. 97—100 С. 1Н NMR, : 0.93 (t, 3
Н, Me, 3JH,H = 6.3 Hz); 1.23—1.43 (m, 18 Н, OCH2СН2(СН2)9);
1.54—1.67 (m, 2 Н, OCH2СН2(CH2)9); 2.93 (d, 6 H, NMe2,
Nꢀ(ꢀBenzyloxyethyl)ꢀNꢀdodecylꢀN,Nꢀdimethylammonium
(3a,b) chlorides (general procedure). A mixture of amine 1a
(4 mmol) and ꢀbenzyloxyethyl chloride 7h,g (4 mmol) in absoꢀ
lute MeCN (3 mL) was refluxed for 20—50 h and then evaporatꢀ
ed in vacuo. The residue was recrystallized. The reaction condiꢀ
tions in each particular case, yields, and physicochemical paraꢀ
meters of quaternary ammonium compounds 3a,b are presented
in Table 3. The data of the 1Н NMR spectra are given in Table 5.
NꢀBenzyloxycarbonylmethylꢀNꢀdodecylꢀN,Nꢀdimethylammoꢀ
nium chloride (4a). A mixture of amine 1a (0.55 g, 2.5 mmol) and
benzyl monochloroacetate 7h (1.85 g, 10 mmol) was kept withꢀ
out stirring at 20—25 С for 1 week. Then, the mixture was dilutꢀ
ed with EtOAc (2 mL), and the formed precipitate was filtered
off and recrystallized (see Tables 3—5).
NꢀBenzylꢀNꢀdodecyloxycarbonylmethylꢀN,Nꢀdimethylammoꢀ
nium chloride (4b). A mixture of amine 1b (1.70 g, 12.5 mmol)
and dodecyl monochloroacetate 7i (1.65 g, 2.5 mmol) was kept
without stirring at 20—25 С for 2 weeks. Then the mixture was
diluted with benzene (1.5 mL), and the formed precipitate was
filtered off and recrystallized (see Tables 3—5).
Alkylation of ethylene glycol with dodecyl bromide according
to the described method.14 Dodecyl bromide (21.6 g, 87 mmol)
was added with stirring to a mixture of ethylene glycol (26.9 g,
435 mmol), a 50% aqueous solution of NaOH (3.5 g, 87 mmol),
and tetrabutylammonium bromide (2.8 g, 8 mmol). After stirring
for 35 h at 100—105 С, the reaction mixture was diluted with
CHCl3 (20 mL) and water (10 mL). The organic layer was sepaꢀ
rated, washed with water (3×10 mL), dried with Na2SO4, and
evaporated in vacuo, and the residue (18.5 g, 93%) was distilled
using Vigreux column. Monoether 8b with b.p. 173—175 С
(12 Torr) was obtained in a yield of 6.0 g (30%). The residue (10.0 g,
58%) was ethylene glycol bisdodecyl ether. 1Н NMR, : 0.85
(t, 6 Н, Me, 3JH,H = 6.5 Hz); 1.18—1.37 (m, 36 Н, Me(СН2)9СН2ꢀ
CH2O); 1.50—1.65 (m, 4 Н, Me(СН2)9СН2CH2O); 3.43 (t, 4 Н,
Me(СН2)9СН2CH2O, 3JH,H = 6.8 Hz); 3.54 (s, 4 Н, ОCH2СН2О).
Ethylene glycol and diethylene glycol monoalkyl ethers 8a—e
(general procedure). Dioxane (15 mL), alkyl halide (25 mmol),
and tetrabutylammonium bromide (0.4 g, 1.2 mmol) were added
3JH,H = 4.9 Hz); 3.29 (q, 2 H, NCH2, 3JH,С,H = 4.7 Hz, 3JH,N,H
=
3
= 3.7 Hz); 3.48 (t, 2 H, OCH2СН2(CH2)9, JH,H = 6.7 Hz);
3.59—3.65 (m,
2 H, NCH2CH2OCH2CH2O); 3.67—3.74
(m, 2 H, NCH2CH2OCH2); 4.02—4.08 (m, 2 H, NCH2CH2O);
12.55—12.76 (m, 1 Н, NH+). Calculated (%): С, 63.97; H, 11.93;
Cl, 10.49; N, 4.14. C18H39NO2•HCl. Found (%): C, 64.15;
H, 12.24; Cl, 10.43; N, 4.06.
NꢀButylꢀNꢀ(2ꢀdodecyloxyethyl)ꢀNꢀmethylamine (6g) was
characterized as its hydrochloride obtained according to the
general procedure in 98% yield, m.p. 82—84 С. 1Н NMR,
3
: 0.92 (t, 3 Н, (СН2)9Me, JH,H = 5.7 Hz); 1.01 (t, 3 Н,
3
NCH2CH2CH2Me, JH,H = 7.3 Hz); 1.20—1.51 (m, 20 Н,
OCH2СН2(СН2)9 + NCH2CH2CH2Me); 1.53—1.67 (m, 2 Н,
NCH2CH2CH2Me); 1.80—1.96 (m, 2 Н, OCH2СН2(СН2)9);
2.87 (br.s, 3 H, NMe); 3.03—3.19 (m, 2 H, NCH2CH2CH2Me);
3.22—3.33 (m, 2 H, NCH2СН2O); 3.49 (t, 2 H, OCH2СН2ꢀ
3
(СН2)9, JH,H = 6.3 Hz); 3.91—4.00 (m, 2 H, NCH2CH2O);
12.22—12.53 (m, 1 Н, NH+). Calculated (%): С, 67.92; H, 12.60;
Cl, 10.55; N, 4.17. C19H41NO•HCl. Found (%): C, 67.89;
H, 12.61; Cl, 10.11; N, 4.35.
NꢀButylꢀNꢀ[2ꢀ(2ꢀdodecyloxyethoxy)ethyl]ꢀNꢀmethylamine
(6h) was characterized as its hydrochloride obtained according
to the general procedure in 97% yield, m.p. 57—59 С. 1Н NMR,
3
: 0.91 (t, 3 Н, (СН2)9Me, JH,H = 6.3 Hz); 1.00 (t, 3 Н,
3
NCH2CH2CH2Me, JH,H = 7.4 Hz); 1.22—1.51 (m, 20 Н,
OCH2СН2(СН2)9 + NCH2CH2CH2Me); 1.53—1.66 (m, 2 Н,
NCH2CH2CH2Me); 1.86 (quintet, 2 Н, OCH2СН2(CH2)9,
3JH,H = 7.9 Hz); 2.87 (br.s, 3 H, NMe); 3.11 (t, 2 H, NCH2CH2ꢀ
3
3
CH2Me, JH,H = 8.2 Hz); 3.28 (t, 2 H, NCH2СН2O, JH,H
=
3
= 4.1 Hz); 3.46 (t, 2 H, OCH2СН2(CH2)9, JH,H = 6.7 Hz);
3.57—3.63 (m, 2 H, NCH2CH2OCH2CH2O); 3.65—3.72 (m, 2 H,
NCH2CH2OCH2); 4.02 (t, 2 H, NCH2CH2O, 3JH,H = 3.9 Hz);
12.01—12.23 (m, 1 Н, NH+). Calculated (%): С, 66.37; H, 12.20;