654
J.W. Guo et al. / Chinese Chemical Letters 23 (2012) 653–656
HCl
N
R
Br-
N
N
N
O
COOH
COCl
a
d
e
c
b
5a-5d
3
2
4
1
Scheme 1. The synthesis of compounds 5a–5d. Condition and regent: (a) SOCl2, 80 8C, 3 h, 99%; (b) TEA, HN(CH3)2.HCl, CH2Cl2, r.t., 12 h, 79%;
(c) i: LiAlH4, dry THF, reflux, 20 h, ii: 2 mol/L HCl, 77% in two steps; (d) 2 mol/L NaOH; and (e) RBr, isopropanol, reflux, 48 h, 26À43%.
80 8C, and became transparent. The excess SOCl2 was removed by distilling to give compound 1. Then to a stirring
suspension of dimethyl amine hydrochloride salt (86 mmol) and triethylamine (TEA) (180 mmol) in CH2Cl2 (50 mL)
was added into the solution of the compound 1 (55 mmol) in CH2Cl2 (25 mL) at 0 8C. The resulting solution was
stirred at r.t. for 12 h, and then the solution was washed by dilute hydrochloric acid and brine. The combined organic
layers were dried (MgSO4), and concentrated to give a light yellow crystalline solid. The solid was purified by column
chromatography (ethyl acetate:hexanes = 1:1) to give compound 2 as a colorless crystalline solid. 1H NMR (300 MHz,
CDCl3): d 1.717 (br s, 6H), 2.019 (br s, 9H), 3.053 (br s, 6H).
N,N-Dimethyl-1-aminomethyladamantane hydrochloride (3) was synthesized by the reduction of compound 2
using LiAlH4 in dry THF and then hydrochlorination with ice cold 2 mol/L HCl. Compound 3 was recrystallized from
1
methanol/acetone to give white crystals, H NMR (300 MHz, D2O): d 1.546–1.554 (m, 6H), 1.591–1.691 (m, 6H),
1.931 (br s, 3H), 2.832 (s, 6H), 2.865 (m, 2H). Then compound 3 was neutralized by 2 mol/L NaOH (25 mL) to give
compound 4 as a colorless transparent liquid.
Finally, a series of 1-(alkyldimethylammoniamethyl) adamantane bromide (5a–5d) were synthesized by
quaternization of compound 4 with n-bromoalkanes. For instance, the 1-(octyldimethylammoniamethyl) adamantane
bromide was synthesized as follows. The solution of 1-bromooctane (13 mmol) in isopropanol was added to a stirred
solution of compound 4 (10 mmol) in isopropanol, the mixture was refluxed for 48 h. Then the resulting mixture was
concentrated. The residue was washed several times with diethyl ether (3 Â 30 mL) to give a colorless crystalline
solid. Then the solid was recrystallized from THF and purified by column chromatography (dichloromethane:-
methanol:ammonia = 15:1:0.01) to give compound 5a as colorless crystals. 5b, 5c and 5d were synthesized via similar
procedures. The results of compounds 5a–5d are listed in Table 1.
Table 1
The results of compounds 5a–5d.
Compound
R
Yield 1H NMR (300 MHz, CDCl3): d
Elements analysis (%, calcd.)
FTIR (KBr, cmÀ1): n
5a
–C8H17
43%
0.858–0.902 (t, 3H), 1.269–1.362 (m, 10H),
1.702–1.725 (m, 8H), 1.828–1.835 (m, 6H),
2.053 (br s, 3H), 3.324 (s, 2H), 3.482 (s, 6H),
3.619–3.676 (t, 2H)
C, 65.27(65.09); H, 10.43(10.48); 2904, 2848, 1632, 1486,
Br, 20.68(20.55); N, 3.62(3.88). 1469, 1458, 1105, 933.
5b
5c
5d
–C10H21 39%
–C12H25 35%
–C16H33 26%
0.855–0.900 (t, 3H), 1.258–1.361 (m, 14H),
1.713–1.733 (m, 8H), 1.810–1.833 (m, 6H),
2.061 (br s, 3H), 3.320 (s, 2H), 3.476 (s, 6H),
3.615–3.671 (t, 2H)
C, 66.64(66.90); H, 10.70(10.63); 2904, 2849, 1631,
Br, 19.28(19.05); N, 3.38(3.42).
1477 1469, 1457,
1103, 932.
0.854–0.898 (t, 3H), 1.250–1.366 (m, 18H),
1.712–1.731 (m, 8H), 1.808––1.834 (m, 6H),
2.059 (br s, 3H), 3.314 (s, 2H), 3.470 (s, 6H),
3.609–3.664 (t, 2H)
C, 67.85(67.98); H, 10.93(10.87); 2905, 2849, 1631,
Br, 18.05(17.87); N, 3.16(3.28).
1477 1469, 1457,
1103, 984.
0.854–0.898 (t, 3H), 1.250–1.358 (m, 26H),
1.699–1.722 (m, 8H), 1.769–1.832 (m, 6H),
2.052 (br s, 3H), 3.322 (s, 2H), 3.482 (s, 6H),
3.615–3.672 (t, 2H)
C, 69.85(70.08); H, 11.32(11.27); 2916, 2849, 1631,
Br, 16.02(15.71); N, 2.81(2.94). 1469, 1457, 1103, 984.