PAPER
Synthesis of Quaternary Alkylammonium Sulfobetaines
2437
moles of H2 being adsorbed. The catalyst was removed by suction
filtration (using celite as a filter aid) and EtOH was removed in vac-
uo to yield the hydrochloride salt of 34 (5.404 g, 95%) as an orange
powder.
1H NMR (400 MHz, CDCl3): = 0.89 (t, 3 H, J = 6.4 Hz, CH3),
1.26–1.40 [m, 6 H, CH3(CH2)3], 1.59 [q5, 2 H, J = 7.1 Hz,
CH3(CH2)3CH2], 2.18 (m, 2 H, CH2CH2N), 2.57 (t, 2 H, J = 7.7 Hz,
ArCH2), 2.70 (t, 2 H, J = 7.2 Hz, ArCH2), 2.78 [s, 6 H, N(CH3)2],
2.96–2.99 (m, 2 H, CH2N), 7.08 and 7.11 (2 d, 4 H, J = 8.0 Hz,
C6H4), 12.27 (br s, 1 H, HCl).
13C NMR (101 MHz, CDCl3): = 14.5 (CH3), 23.0 (CH3CH2), 26.0
(CH2CH2N), 29.4 (CH2), 31.9 (CH2), 32.1 (CH2), 32.5 (ArCH2),
35.9 (CH2Ar), 43.3 (NCH3), 57.8 (CH2N), 128.6 (Ar, CH), 129.2
(Ar, CH), 136.7 (Ar, C-1/4), 141.7 (Ar, C-1/4).
MS-EI: m/z = 247 (100%) [M+], 202 (18%), 189 (14%), 175 (16%).
MS-CI: m/z = 248 (100%) [M + H]+, 131 (3%).
tered, washed with Et2O, and dried in vacuo to yield 13 (10.906 g,
63%) as a white crystalline solid; mp 260–262 °C.
1H NMR (400 MHz, CD3OD): = 0.90–0.96 (m, 3 H, CH3), 1.34–
1.41 [m, 6 H, CH3(CH2)3], 1.79 (m, 2 H, CH2CH2N), 1.84 (q5, 2 H,
J = 7.1 Hz, CH2CH2SO3), 1.90–1.99 (m, 2 H, NCH2CH2), 2.89 (t, 2
H, J = 7.1 Hz, CH2SO3), 3.07 [s, 6 H, N(CH3)2], 3.29 (m, 2 H,
CH2N), 3.34 (m, 2 H, NCH2).
13C NMR (101 MHz, CD3OD): = 14.4 (CH3), 22.3, 23.0, 23.5 (3
CH2), 23.5 (CH2CH2SO3), 27.1 (NCH2CH2), 32.4 (CH2CH2N),
51.2 (NCH3), 51.3 (CH2SO3), 64.9 (NCH2), 65.6 (CH2N).
MS-EI: m/z = 265 (2%) [M+], 264 (15%) [M–H]+, 194 (40%), 180
(20%), 137 (30%), 129 (100%), 128 (80%).
MS-CI: m/z = 266 [M + H]+, 2%), 252 (3%), 170 (7%), 168 (4%),
154 (79%), 131 (13%), 130 (100%).
HRMS: m/z calcd for C12H28NSO3 [M + H]+, 266.1790; found,
266.1788.
HRMS: m/z calcd for C17H29N [M]+, 247.2300; found, 247.2300.
N-Heptyl-N,N-dimethyl-4-ammonio-1-butanesulfonate (14)
Prepared using the procedure described above starting from N,N-
dimethylheptylamine (9.545 g, 66.7 mmol). The product 14 was ob-
tained as a white crystalline solid (13.566 g, 73%); mp 252–253 °C.
1H NMR (400 MHz, CD3OD): = 0.81 (t, 3 H, J = 6.8 Hz, CH3),
1.20–1.30 [m, 8 H, CH3(CH2)4], 1.61–1.68 (m, 2 H, CH2CH2N),
1.72 (q5, 2 H, J = 7.2 Hz, CH2CH2SO3), 1.79–1.86 (m, 2 H,
NCH2CH2), 2.76 (t, 2 H, J = 7.2 Hz, CH2SO3), 2.95 [s, 6 H,
N(CH3)2], 3.18 (m, 2 H, CH2N), 3.23 (m, 2 H, NCH2).
13C NMR (101 MHz, CD3OD): = 14.3 (CH3), 22.3 (CH2), 23.0
(CH2), 23.5 (CH2), 23.5 (CH2CH2SO3), 27.3 (NCH2CH2), 29.9
(CH2), 32.7 (CH2CH2N), 51.0 (NCH3), 51.1 (CH2SO3), 64.8
(NCH2), 65.4 (CH2N).
The hydrochloride salt (5.310 g, 18.8 mmol) was quenched with a
sat. aq Na2CO3 until a pH of ~10 was reached (confirmed by indi-
cator paper). Extraction with EtOAc (3 50 mL) and removal of the
solvent in vacuo yielded 34 (4.495 g, 97%) as a brown oil.
1H NMR (400 MHz, CDCl3): = 0.81 (t, 3 H, J = 6.7 Hz, CH3),
1.17–1.29 [m, 6 H, CH3(CH2)3], 1.52 [q5, 2 H, J = 7.5 Hz,
CH3(CH2)3CH2], 1.71 (q5, 2 H, J = 7.7 Hz, CH2CH2N), 2.15 [s, 6 H,
N(CH3)2], 2.23 (t, 2 H, J = 7.5 Hz, CH2N), 2.49 (t, 2 H, J = 7.9 Hz,
ArCH2), 2.52 (t, 2 H, J = 7.7 Hz, ArCH2), 7.02 (s, 4 H, C6H4).
13C NMR (101 MHz, CDCl3): = 14.5 (CH3), 23.0 (CH3CH2), 29.9
(CH2CH2N), 30.0 (CH2), 32.0 (CH2), 33.0 (CH2), 33.7 (ArCH2),
36.0 (CH2Ar), 45.9 (NCH3), 59.8 (CH2N), 128.6 (Ar, CH), 128.7
(Ar, CH), 139.8 (Ar, C-1/4), 140.7 (Ar, C-1/4).
MS-EI: m/z = 279 (1%) [M+], 278 (2%) [M – H]+, 194 (5%), 180
N-[3-(4-Hexylphenyl)propyl]-N,N-dimethyl-3-ammonio-1-pro-
panesulfonate (12)
Prepared using the procedure described above starting from 34
(2.090 g, 8.5 mmol). The product 12 was obtained as an off-white
crystalline solid (1.286 g, 41%).
(5%), 144 (18%), 143 (100%), 142 (30%).
MS-CI: m/z = 280 (2%) [M + H]+, 266 (1%), 196 (2%), 184 (11%),
154 (59%), 144 (100%), 130 (33%).
HRMS: m/z calcd for C13H30NSO3 [M + H]+, 280.1946; found,
280.1942.
1H NMR (400 MHz, CDCl3): = 0.89 (t, 3 H, J = 6.7 Hz, CH3),
1.30–1.34 [m, 6 H, CH3(CH2)3], 1.58 [q5, 2 H, J = 7.3 Hz,
CH3(CH2)3CH2], 2.06–2.17 (m, 4 H, CH2CH2SO3 and CH2CH2N),
2.56 (t, 2 H, J = 7.4 Hz, ArCH2), 2.68 (t, 2 H, J = 7.5 Hz, ArCH2),
2.86 (t, 2 H, J = 6.8 Hz, CH2SO3), 3.07 [s, 6 H, N(CH3)2], 3.28–3.34
(m, 2 H, CH2N), 3.50 (m, 2 H, NCH2), 7.11 and 7.17 (2 d, 4 H,
J = 8.1 Hz, C6H4).
13C NMR (101 MHz, CDCl3): = 14.4 (CH3), 19.8 (NCH2CH2),
23.7 (CH3CH2), 25.3 (CH2CH2N), 30.0 (CH2), 32.8 (CH2), 32.8
(CH2), 32.9 (ArCH2), 36.5 (CH2Ar), 48.6 (CH2SO3), 51.3 (NCH3),
63.7 (NCH2), 65.0 (CH2N), 129.4 (Ar, CH), 129.7 (Ar, CH), 138.4
(Ar, C-1/4), 142.2 (Ar, C-1/4).
N-Octyl-N,N-dimethyl-4-ammonio-1-butanesulfonate (15)
To a stirred soln of 1,4-butanesultone (7.696 g, 56.6 mmol) in
EtOAc (20 mL), was added a soln of N,N-dimethyloctylamine
(8.881 g, 56.6 mmol) in EtOAc (20 mL). The reaction mixture was
stirred under reflux for 2.5 h. After cooling, the resulting white pre-
cipitate was filtered, washed with Et2O, and dried in vacuo yielding
15 (10.465 g, 63%) as a white crystalline solid; mp 251–252 °C.
1H NMR (400 MHz, CD3OD): = 0.81 (t, 3 H, J = 6.8 Hz, CH3),
1.18–1.32 [m, 10 H, CH3(CH2)5], 1.62–1.70 (m, 2 H, CH2CH2N),
1.73 (q5, 2 H, J = 7.2 Hz, CH2CH2SO3), 1.80–1.88 (m, 2 H,
NCH2CH2), 2.78 (t, 2 H, J = 7.2 Hz, CH2SO3), 2.98 [s, 6 H,
N(CH3)2], 3.20 (m, 2 H, CH2N), 3.25 (m, 2 H, NCH2).
(MS-ES+): m/z = 761 (2%) [2M + Na]+, 739 (10%) [2M + H]+, 392
(11%) [M + Na]+, 370 (100%) [M + H]+, 248 (13%).
13C NMR (101 MHz, CD3OD): = 14.4 (CH3), 22.3 (CH2), 23.0
(CH2), 23.5 (CH2), 23.6 (CH2CH2SO3), 27.4 (NCH2CH2), 30.2
(CH2), 30.2 (CH2), 32.8 (CH2CH2N), 51.1 (NCH3), 51.4 (CH2SO3),
64.8 (NCH2), 65.4 (CH2N).
(MS-ES–): m/z = 797 (8%) [2M + AcO]–, 526 (8%), 428 (100%) [M
+ AcO]–, 404 (8%) [M + Cl]–, 315 (15%), 157 (45%).
HRMS (ES+): m/z calcd for C20H36NSO3 [M + H]+, 370.2416;
found, 370.2420.
MS-EI: m/z = 293 (1%) [M+], 292 (32%) [M – H]+, 280 (8%), 194
(34%), 180 (50%), 156 (100%).
Butane Sulfobetaines 13–21
MS-CI: m/z = 294 (3%) [M + H]+, 280 (4%), 198 (15%), 196 (10%),
158 (100%), 154 (54%), 144 (34%).
HRMS: m/z calcd for C14H32NSO3 [M + H]+, 294.2103; found,
294.2100.
N-Hexyl-N,N-dimethyl-4-ammonio-1-butanesulfonate (13)
To a stirred soln of 1,4-butanesultone (8.941 g, 65.7 mmol) in
EtOAc (30 mL), was added N,N-dimethylhexylamine (9.470 g, 73.4
mmol) in EtOAc (30 mL). The reaction mixture was stirred under
reflux for 44 h. After cooling, the resulting white precipitate was fil-
Synthesis 2002, No. 16, 2431–2439 ISSN 0039-7881 © Thieme Stuttgart · New York