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L. Caillier et al. / European Journal of Medicinal Chemistry 44 (2009) 3201–3208
4.75 (2H, NþCH2CH2OC(O), m), 5.92 (1H, CH]CH2
,
3J ¼ 10.28,
against C. albicans where the cut off effect seems centred on
H$2$14.
- The recorded MLC values are systematically lower for the
surfactants with an undecylenic spacer (H$11$n).
cis
2J ¼ 1.68, dd), 6.15 (1H, CH]CH2, dd, 3J ¼ 10.28, 3J ¼ 17.18, dd), 6.45
(1H, CH]CH2
,
3J ¼ 17.18, 2J ¼ 1.68, dd), 7.61 (5H, Bz, m). 13C
trans
NMR (200 MHz, MeOD,
d
ppm): 52.2 (NþCH3), 59.3 (NþCH2CH2O),
65.0 (NþCH2CH2O), 69.8 (NþCH2C6H5), 128.6 (OC(O)CH]CH2),
129.2, 131.2, 132.4 (CHAr), 132.9 (OC(O)CH]CH2), 135.4 (CAr), 166.4
(OC(O)CH]CH2). MS, [M-Br]þ, m/z: 234.2; Anal. Calcd for
C14H20BrNO2: C 53.51, H 6.42, N 4.46; found: C 53.54, H 6.39, N
4.45.
- The benzylic derivatives present the worst activities. H$2$Bz
showing only an activity towards A. niger.
3. Experimental section
3.1. Chemical synthesis
3.1.3.2. Compound 2. 1H NMR (MeOD,
d ppm, J Hz): 0.85 (3H,
3.1.1. General
CH3CH2, t), 1.26 (14H, CH3(CH2)7CH2, m), 1.76 (2H, C8H17CH2CH2Nþ,
m), 3.13 (6H, NþCH3, s), 3.37 (2H, C8H17CH2CH2Nþ, m), 3.69 (2H,
NþCH2CH2OC(O), m), 4.57 (2H, NþCH2CH2OC(O), m), 5.92 (1H,
Confirmation of the structures of the intermediates and prod-
ucts was obtained by nuclear magnetic resonance (NMR), mass
spectrometry (MS) and infrared spectroscopy (FT IR). NMR spec-
troscopy was carried out using a Bruker Advance 200 MHz or 500
spectrometer. MS was carried out using a Finnigan Matt TSQ 7000
mass spectrometer coupled with a gas chromatograph or liquid
chromatography interface. Infrared spectroscopy was carried out
using a Perkin Elmer Paragon 1000 FT IR spectrometer. Gas phase
chromatography was done from Hewlett PackardÔ HP 5890 Series
II GC with HP5 colꢀu1mn 30 m, 0.32 diameter, from 60 to 250 ꢁC at
CH]CH2
,
3J ¼ 10.28, 2J ¼ 1.68, dd), 6.15 (1H, CH]CH2, dd,
cis
3J ¼ 10.28, 3J ¼ 17.18, dd), 6.45 (1H, CH]CH2
,
3J ¼ 17.18,
trans
2J ¼ 1.68, dd). 13C NMR (200 MHz, MeOD,
d
ppm): 15.1
(CH3CH2CH2), 24.0 (CH3CH2CH2 and CH2CH2Nþ), 28–30.0 (5C,
CH3CH2CH2(CH2)5), 33.5 (CH3CH2CH2), 52.2 (NþCH3), 59.3
(NþCH2CH2O), 64.6 (CH2CH2Nþ), 65.0 (NþCH2CH2O), 128.6
(OC(O)CH]CH2), 132.9 (OC(O)CH]CH2), 166.4 (OC(O)CH]CH2).
MS, [M-Br]þ, m/z: 284.3; Anal. Calcd for C17H34BrNO2: C 56.04, H
9.41, N 3.84; found: C 56.04, H 9.51, N 3.83.
a rate of 10 ꢁC min
.
Benzyl bromide, 1-bromodecane, 1-bromododecane, 1-bromo-
tetradecane, 1-bromohexadecane, 11-bromo-1-undecanol, 2-
(dimethylamino)ethyl acrylate were purchased from Aldrich and
used as-received. Dimethylamine solution (33% in absolute
ethanol) and acryloyl chloride were purchased from Fluka Chem-
icals. All other reagents employed were common laboratory
materials. Unless specified the solvents were of unpurified reagent
grade.
3.1.3.3. Compound 3. 1H NMR (200 MHz, MeOD,
0.84 (3H, CH3CH2, t), 1.24 (18H, CH3(CH2)9CH2 CH2, m), 1,74
d ppm, J Hz):
(2H, C10H
21CH2CH2Nþ, m), 3.15 (6H, NþCH3, s), 3.38 (2H,
C10H21CH2CH2Nþ, m), 3.70 (2H, NþCH2CH2OC(O), m), 4.56
(2H, NþCH2CH2OC(O), m), 5.89 (1H, CH]CH2 cis, 3J ¼ 10.32, 2J ¼ 1.59,
dd), 6.13 (1H, CH]CH2, dd, 3J ¼ 10.32, 3J ¼ 17.35, dd), 6.46 (1H,
CH]CH2 trans
d
,
3J ¼ 17.35, 2J ¼ 1.59, dd). 13C NMR (200 MHz, MeOD,
ppm): 15.1 (CH3CH2CH2), 24.0 (CH3CH2CH2 and CH2CH2Nþ), 28–
3.1.2. Synthesis of 11-(dimethylamino)undecyl acrylate
30.0 (7C, CH3CH2CH2(CH2)7), 28–30.0 (7C, CH3CH2CH2(CH2)7), 33.5
(CH3CH2CH2), 52.2 (NþCH3), 59.3 (NþCH2CH2O), 64.6 (CH2CH2Nþ),
65.0 (NþCH2CH2O), 128.6 (OC(O)CH]CH2), 132.9 (OC(O)CH]CH2),
166.4 (OC(O)CH]CH2). MS, [M-Br]þ, m/z: 312.3; Anal. Calcd for
C19H38BrNO2: C 58.15, H 9.76, N 3.57; found: C 58.12, H 9.79, N 3.51.
3.1.2.1. Step i. 50 mmol of dimethylamine in ethanol were added
dropwise to 10 mmol of 11-bromoundecan-1-ol in ethanol. After
6 h, the initial brominated compound was completely consumed.
The excess of ethanol and amine was removed under reduce
pressure. The crude product was dissolved in dichloromethane and
washed three times using a 5% NaHCO3 water solution. The solvent
was removed on reduced pressure. The final product was used
without any further purification. (Yield: 91%).
3.1.3.4. Compound 4. 1H NMR (MeOD,
(3H, CH3CH2, t), 1.23 (22H, CH3(CH2)11CH2CH2, m), 1.71 (2H,
d ppm, J Hz): 0.92
C12H
25CH2CH2Nþ, m), 3.11 (6H, NþCH3, s), 3.35 (2H,
C12H25CH2CH2Nþ, m), 3.67 (2H, NþCH2CH2OC(O), m), 4.61
(2H, NþCH2CH2OC(O), m), 5.93 (1H, CH]CH2 cis, 3J ¼ 10.25, 2J ¼ 1.65,
dd), 6.16 (1H, CH]CH2, dd, 3J ¼ 10.25, 3J ¼ 16.98, dd), 6.49 (1H,
3.1.2.2. Step ii. To a stirred solution of 10 mmol of 11-(dimethy-
lamino)undecan-1-ol, in anhydrous acetonitrile (10 mL), under
inert atmosphere (N2) and at the temperature of 0 ꢁC, 10 mmol of
acryloyl chloride was added dropwise. The solution was main-
tained at 0 ꢁC for 2 h and then stirred for 12 h at room
temperature.
The solution was then neutralized with a 5% NaHCO3 water
solution. The water/acetonitrile solution was extracted five times
with dichloromethane. The organic phase was dried under Na2SO4
and the solvent evaporated. The final acrylic product was used
without any further purification. (Yield: 82%).
CH]CH2 trans
d
,
3J ¼ 16.98, 2J ¼ 1.65, dd). 13C NMR (200 MHz, MeOD,
ppm): 15.3 (CH3CH2CH2), 24.2 (CH3CH2CH2 and CH2CH2Nþ), 28.1–
30.0 (9C, CH3CH2CH2(CH2)9), 33.6 (CH3CH2CH2), 52.3 (NþCH3), 59.2
(NþCH2CH2O), 64.5 (CH2CH2Nþ), 65.2 (NþCH2CH2O), 128.8
(OC(O)CH]CH2), 132.7 (OC(O)CH]CH2), 166.1 (OC(O)CH]CH2).
MS, [M-Br]þ, m/z: 340.3; Anal. Calcd for C21H42BrNO2: C 59.99, H
10.07, N 3.33; found: C 60.02, H 10.16, N 3.36.
3.1.3.5. Compound 5. 1H NMR (MeOD,
d
ppm, J Hz): 0.84 (3H, CH3CH2
29CH2CH2Nþ, m),
t), 1.22 (26H, CH3(CH2)13CH2CH2, m), 1.73 (2H, C14
H
3.1.3. Formation of the polymerizable hydrocarbon surfactants
1 mol of alkyl bromide or benzylbromide reacted with 1.5 mol of
acrylic precursor, in solvent-free conditions, for 12 h, at a temper-
ature of 50 ꢁC and in the presence of 0.05% of hydroquinone. The
crude gum obtained was purified by multiple trituration in cyclo-
hexane. The quaternary ammonium compound was finally dried
under vacuum for 72 h. Yields: from 88 to 96% depending with the
length of the alkyl chains.
3.11 (6H, NþCH3, s), 3.34 (2H, C14H29CH2CH2Nþ, m), 3.73 (2H,
NþCH2CH2OC(O), m), 4.45 (2H, NþCH2CH2OC(O), m), 5.91 (1H,
CH]CH2
,
3J ¼ 10.23, 2J ¼ 1.72, dd), 6.11 (1H, CH]CH2, dd,
cis
3J ¼ 10.23, 3J ¼ 17.21, dd), 6.47 (1H, CH]CH2 trans, 3J ¼ 17.21, 2J ¼ 1.72,
dd). 13C NMR (200 MHz, MeOD,
d ppm): 15.0 (CH3CH2CH2), 24.2
(CH3CH2CH2 andCH2CH2Nþ), 28–30.0 (11C, CH3CH2CH2(CH2)11), 33.3
(CH3CH2CH2), 52.1 (NþCH3), 59.4 (NþCH2CH2O), 64.8 (CH2CH2Nþ),
65.2 (NþCH2CH2O), 128.1 (OC(O)CH]CH2), 132.2 (OC(O)CH]CH2),
166.1 (OC(O)CH]CH2). MS, [M-Br]þ, m/z: 368.4; Anal. Calcd
for C23H46BrNO2: C 61.59, H 10.34, N 3.12, found: C 61.59, H 10.29,
N 3.13.
3.1.3.1. Compound 1. 1H NMR (200 MHz, MeOD,
(6H, NþCH3, s), 3.86 (2H, NþCH2CH2OC(O), m), 4.74 (2H, BzCH2Nþ, s),
d ppm, J Hz): 3.20