O-Substituted hydroxylamines from alcohols
511
28.38, 21.38. Calculated, %: C 44.93; H 7.92; N 5.24.
C10H21NO5S. Found, %: C 44.98; H 7.98; N 5.17.
(1g)—Yield 91.1%; bp 125–126°C/0.7 mmHg. 1H NMR
(CDCl3): d 4.22 (2H, t, J 6.6); 3.53 (2H, t, J 6.5); 3.00 (3H, s);
1.81–1.75 (4H, m); 1.52–1.39 (4H, m). 13C NMR (CDCl3):
d 69.84, 44.82, 37.39, 32.31, 29.00, 26.27, 24.79. Found,
%: C 39.25; H 6.97. C7H15ClO3S. Calculated, %: C 39.16;
H 7.04.
J 7.2); 3.86 (4H, t, J 6.6); 1.91 (6H, s); 1.65–1.59 (4H, m);
1.39–1.36 (4H, m); 1.25 (6H, t, J 7.2). 13C NMR (CDCl3):
d 162.13, 73.54, 62.09, 28.09, 26.00, 14.41, 13.60. Calcu-
lated, %: C 58.31; H 9.79; N 9.71. C14H28N2O4. Found, %:
C 58.54; H 9.80; N 9.73.
(2f)—Reaction time 48 h; yield 68.6%; self-crystallized
1
oil, solid has mp 38°C. Rf 0.67 (CHCl3–MeOH, 98:2); H
NMR (CDCl3): d 4.63 (1H, s); 4.03–3.93 (4H, m); 3.78
(1H, bs); 1.94 (3H, s); 1.84–1.70 (2H, m); 1.44 (9H, s);
1.26 (3H, t, J 7.1); 1.17 (3H, d, J 6.6). 13C NMR (CDCl3):
d 162.36, 155.34, 78.88, 70.63, 62.20, 44.70, 35.73, 28.44,
21.18, 14.39, 13.73. Calculated, %: C 56.91; H 9.55; N
10.21. C13H26N2O4. Found, %: C 57.06; H 9.69; N 10.05.
(2g)—Reaction time 96 h; yield 82%; bp 72–73°C/
General method of ethyl N-hydroxyacetimidate
alkylation with alkyl methanesulfonates
To a stirred 2 M solution of sodium salt of ethyl
N-hydroxyacetimidate (ethyl N-hydroxyacetimidate from
‘‘Aldrich’’ was distilled before use, bp 62°C/12 mmHg) in
MeOH or i-PrOH, an equivalent of the corresponding alkyl
methanesulfonate was added slowly in small portions and
stirring was continued at 20°C until the neutral pH of the
reaction mixture. Precipitate was filtered off, filtrate was
evaporated to dryness in vacuo, and the residue was poured
into water and extracted with CHCl3 (Et2O was used in the
case of 2a and 2b). Combined organic extracts were
washed with 1 M NaHCO3, H2O, brine, dried (MgSO4),
and evaporated to dryness in vacuo, affording ethoxye-
thylidene derivatives (2a)–(2g):
1
0.7 mmHg; n2D0 1.4475. H NMR (CDCl3): 4.00 (2H, q,
J 7.2); 3.87 (2H, t, J 6.5); 3.52 (2H, t, J 6.9); 1.91 (3H, s);
1.81–1.74 (2H, m); 1.66–1.59 (2H, m); 1.50–1.34 (4H, m);
1.26 (3H, t, J 7.2).13C NMR (CDCl3): d 162.16, 73.35,
62.11, 45.03, 32.61, 28.76, 26.78, 25.45, 14.41, 13.61.
Calculated, %: C 54.17; H 9.09; N 6.32. C10H20ClNO2.
Found, %: C 54.28; H 9.11; N 6.18.
General procedure for the removal of ethoxyethylidene
protection of aminooxy group
(2a)—Reaction time 16 h; yield 78%; bp 91–91.5°C/
47 mmHg; n2D0 1.4178 (lit. (Nedospasov and Khomutov
1976): bp 64°C/14 mmHg, n1D6 1.4216). 1H NMR (CDCl3):
d 3.99 (2H, q, J 6.9); 3.86 (2H, t, J 6.5); 1.90 (3H, s); 1.62–
1.55 (2H, m); 1.41–1.31 (2H, m); 1.25 (3H, t, J 6.9); 0.91
(3H, t).
To the solution of 1 equiv. of ethyl N-alkoxyacetimidate’s
(2a)–(2e), and (2g) in i-PrOH was added 2.5 equiv. of 37%
aq. HCl and after 3–5 min at 20°C, the reaction mixture
was evaporated to dryness in vacuo. The residue was
co-evaporated twice with abs. i-PrOH and crystallized from
i-PrOH–Et2O that after drying in vacuo over P2O5/KOH
yielded compounds (3a)–(3e), and (3g):
(2b)—Reaction time 36 h; yield 65%; bp 74–74.5°C/
72 mmHg; n2D0 1.4096. 1H NMR (CDCl3): d 4.13–4.09 (1H,
m); 4.01 (2H, q, J 7.1); 1.90 (3H, s); 1.27 (3H, t, J 7.1);
1.12 (6H, d, J 6.2). 13C NMR (CDCl3): d 161.71, 74.45, 61.97,
21.51, 14.44, 13.66. Calculated, %: C 57.90; H 10.41; N 9.65.
C7H15NO2. Found, %: C 58.18; H 10.45; N 9.55.
(3a)—Yield 97%; mp 157°C (lit. Theilacker and Ebke
1956): mp 159–160°C).
(3b)—Yield 87%; mp 85–86°C (lit. Theilacker and
Ebke 1956): mp 84.8°C).
(3c)—Yield 86%; mp 184–185°C, dec. (lit. Albrecht et al.
2006): mp 210–220°C, subl. at 176–178°C; (lit. Theilacker
(2c)—Reaction time 7 days; yield 57.6%; bp 94–96°C/
1
1
12 mmHg; n2D0 1.4512. H NMR (CDCl3): d 4.01 (2H, q,
and Ebke 1956): mp 175°C. H NMR (D2O): d 4.09–4.00
J 7.1); 3.86–3.80 (1H, m); 1.93 (3H, s); 1.91–1.89 (2H, m);
1.72–1.68 (2H, m); 1.54–1.49 (1H, m); 1.41–1.21 (5H, m);
1.26 (3H, t, J 7.1). 13C NMR (CDCl3): d 161.89, 79.77,
61.99, 31.62, 25.98, 23.90, 14.46, 13.67. Calculated, %: C
64.83; H 10.34; N 7.56. C10H19NO2. Found, %: C 64.88;
H 10.44; N 7.62.
(1H, m), 1.98–1.89 (2H, m), 1.75–1.66 (2H, m), 1.53–1.45
(1H, m), 1.43–1.14 (5H, m). 13C NMR (D2O): d 86.13,
32.37, 27.25, 25.52. Calculated, %: C 47.53; H 9.31; N 9.24.
C6H14ClNO. Found, %: C 47.38; H 9.49; N 9.17.
(3d)—Yield 91%; mp 188–189°C (lit. Lee et al. 1995):
mp 191°C). 1H NMR (D2O): 7.46–7.42 (5H, m); 5.11
(2H, s); 4.11 (2H, t, J 6.1); 3.23 (2H, t, J 6.5); 1.89–1.84
(2H, m). 13C NMR (CDCl3): d 161.30, 139.34, 131.65,
131.24, 130.53, 75.66, 69.76, 39.67, 30.26.
(2d)—Reaction time 12 h; yield quant.; Rf 0.78 (CHCl3–
1
MeOH, 100:1); H NMR (CDCl3): d 7.37–7.27 (5H, m);
5.09 (3H, m); 3.99 (2H, q, J 7.2); 3.96 (2H, t, J 6.2); 3.35–
3.27 (2H, m); 1.90 (3H, s); 1.88–1.79 (2H, m); 1.25 (3H, t,
J 7.2). (2d) was used without isolation for the preparation
of (3d).
1
(3e)—Yield 93%; mp 227°C, dec. (MeOH–i-PrOH). H
NMR (D2O): d 4.02 (4H, t, J 6.4), 1.69–1.56 (4H, m),
1.41–1.30 (4H, m). 13C NMR (D2O): d 78.22, 29.42, 27.05.
Calculated, %: C 32.59; H; 8.20; N 12.67. C6H18Cl2N2O2.
Found, %: C 32.72; H 8.31; N 12.54.
(2e)—Reaction time 96 h; yield 70.5%; bp 121–122°C/
1
1 mmHg; n2D0 1.4480. H NMR (CDCl3): d 3.99 (4H, q,
123