E
A. Banan et al.
Letter
Synlett
mL) and the product was extracted with CH2Cl2 or EtOAc (3 × 5
mL). The combined organic layers were dried (Na2SO4), filtered,
and concentrated under reduced pressure.
54.92 (–CH2 –).
N,N-Diallylhydroxylamine (1e)
Brown liquid; isolated yield: 503 mg (89%). 1H NMR (CDCl3):
δ = 3.56 (d, J = 6.50 Hz, 4 H, –CH2–N), 5.45 (t, 1J = 2J = 9.25 Hz, 4
H, =CH2), 6.03 (m, 2 H, =CH–), 9.76 (br s, 1 H, NOH). 13C NMR
(CDCl3): δ = 48.02 (–CH2–), 123.98 (=CH2), 128.75 (–CH=).
Morpholin-4-ol (1f)
(38) Zajac, W. W. Jr.; Walters, T. R.; Darcy, M. G. J. Org. Chem. 1988,
53, 5856.
(39) Roffia, P.; Tonti, S.; Cesana, A.; Mantegazza, M. A.; Padovan, M.
US 4918194, 1990.
(40) Laus, G.; Kahlenberg, V. Crystals 2012, 2, 1492.
(41) Wong, A.; Kuethe, J. T.; Davies, I. W. J. Org. Chem. 2003, 68, 9865.
(42) Watson, A. A. J. Org. Chem. 1977, 42, 1610.
(43) Kawasaki, T.; Kodama, A.; Nishida, T.; Shimizu, K.; Somei, M.
Heterocycles 1991, 32, 221.
Brown oily liquid; isolated yield: 329 mg (64%). 1H NMR
(DMSO-d6): δ = 3.19 (t, J = 4.75 Hz, 4 H, –CH2–N), 3.66 (t, J = 4.75
Hz, 4 H, –CH2–O), 10.11 (br s, 1 H, NOH). 13C NMR (CDCl3):
δ = 58.7 (–CH2–N), 65.9 (–CH2–O).
Piperidin-1-ol (1g)
(44) Cicchi, S.; Hold, I.; Brandi, A. J. Org. Chem. 1993, 58, 5274.
(45) Nikbakht, F.; Heydari, A.; Saberi, D.; Azizi, K. Tetrahedron Lett.
2013, 54, 6520.
Brown solid; isolated yield: 460 mg (91%); mp 32–34 °C. 1H
NMR (CDCl3): δ = 1.66 (br s, 2 H, CH2), 1.88 (br s, 4 H, CH2), 3.16
(br s, 4 H, CH2–N), 9.33 (br s, 1 H, NOH). 13C NMR (CDCl3):
δ = 22.34, 22.37, 44.37.
(46) Hale, J. R. US 20150159072, 2015.
(47) Gupte, K.; Coburn, C. E.; Dhamdhere, M. S.; Sawant, M. US
9234052, 2016.
(48) Butler, G. Cyclopolymerization and Cyclocopolymerization;
Dekker: New York, 1992.
(49) Allan, G. G.; Chopra, C. S.; Mattila, T. Pestic. Sci. 1972, 3, 153.
(50) Nicolaou, K. C.; Lee, S. H.; Estrada, A. A.; Zak, M. Angew. Chem.
2005, 117, 3802.
(51) Chittick, E. J.; Stamper, M. A.; Beasley, J. F.; Lewbart, G. A.;
Horne, W. A. J. Am. Vet. Med. Assoc. 2002, 221, 1019.
(52) Ketamine and Medetomidine Free Bases
Pyrrolidin-1-ol (1h)
Brown oily liquid; isolated yield: 313 mg (72%). 1H NMR
(CDCl3): δ = 2.01 (br s, 4 H, CH2), 3.31 (br s, 4 H, CH2–N), 9.58 (br
s, 1 H, NOH). 13C NMR (CDCl3): δ = 24.31 (–CH2–), 44.96 (–CH2–N).
1H-Imidazol-1-ol (1i)
Light-yellow liquid; isolated yield: 310 mg (74%). 1H NMR
(CDCl3): δ = 7.13 (br s, 2 H, CH–N), 7.27 (br s, 1 H, N–CH–N),
7.76 (br s, 1 H, NOH). 13C NMR (CDCl3): δ = 121.62, 135.02.
1H-Indol-1-ol (1j)
Brown oily liquid; isolated yield: 638 mg (96%). 1H NMR
(CDCl3): δ = 6.54 (br s, 1 H, CH-3), 7.12 (t, J = 6.75 Hz, 1 H, CH-5),
7.15 (br s, 1 H, CH-2), 7.19 (t, J = 6.75 Hz, 1 H, CH-6), 7.37 (d, J =
7.75 Hz, 1 H, CH-7), 7.65 (d, J = 7.75 Hz, 1 H, CH-4), 8.18 (br s, 1
H, NOH). 13C NMR (CDCl3): δ = 102.4 (C-3), 111.0 (C-7), 119.7
(C-6), 120.7 (C-4), 121.9 (C-5), 124.2 (C-2), 127.7 (C-9) 135.7 (C-
8).
Ketamine or medetomidine hydrochloride (5 g) was neutralized
with 1 M aq NaHCO3 (25 mL), and the solution was extracted
with CH2Cl2 (3 × 20 mL). The combined extracts were dried
(Na2SO4) and vacuum filtered. The solvent was removed under
reduced pressure to give a pale-yellow powder. The structure
was confirmed by melting-point comparison and by 1H NMR
spectroscopy.
6-Amino-9H-purin-9-ol (1k)
(53) Denney, D. B.; Denney, D. Z. J. Am. Chem. Soc. 1960, 82, 1389.
(54) N,N-Dibenzylhydroxylamine (1a)
Plum powder; isolated yield: 664 mg (88%); mp 210–212 °C.
1H NMR (DMSO-d6): δ = 7.88 (br s, 2 H, NH2), 8.25 (s, 2 H, –CH–)
4.55 (br s, 1 H, –OH). 13C NMR (CDCl3): δ = 112.56 (C-5), 140.96
(C-8), 149.87 (C-4), 150.72 (C-2), 153.80 (C-6).
White powder; isolated yield: 970 mg (91%); mp 122–124 °C.
1H NMR (DMSO-d6): δ = 4.18 (s, 4 H, CH2–), 7.47–7.63 (m, 10 H,
C6H5–), 9.93 (br s, 1 H, N-OH). 13C NMR (DMSO-d6): δ = 50.07 (–
CH2–), 129.01 (C-4), 129.29 (C-3), 130.57 (C-2), 132.33 (C-1, C–
CH2–N–).
4-[1-(2,3-Dimethylphenyl)ethyl]-1H-imidazol-1-ol (1l)
Yellow solid; isolated yield: 897 mg (83%); mp 188–190 °C.
1H NMR (CDCl3): δ = 1.68 (d, J = 7.00 Hz, 3 H, CH3), 2.22 (s, 3 H,
CH3), 2.29 (s, 3 H, CH3), 4.58 (q, J = 7.00 Hz, 1 H, CH), 6.70 (s, 1 H,
N-Benzyl-N-(tert-butyl)hydroxylamine (1b)
White powder; isolated yield: 788 mg (88%); mp 70–72 °C.
1H NMR (DMSO-d6): δ = 1.46 (s, 9 H), 4.13 (s, 2 H), 9.29 (br s, 1
H, N-OH, exchangeable with D2O). 13C NMR (DMSO-d6):
δ = 25.30, 53.39, 56.95, 128.76, 129.94, 130.47, 133.10.
N,N-Diethylhydroxylamine (1c)
CH), 7.01–7.08 (m, 3 H), 8.77 (s, 1 H), 14.41 (br s, 1 H, NOH). 13
C
NMR (CDCl3): δ = 14.9 (CH3), 20.52 (CH3), 20.94 (CH3), 32.18
(CH), 115.14 (CH), 123.91 (CH), 125.89 (CH), 128.94 (CH),
132.90 (quat C), 134.21 (quat C), 137.31 (CH), 138.57 (quat C),
139.49 (quat C).
Brown liquid; isolated yield: 418 mg (94%). 1H NMR (CDCl3):
δ = 1.43 (t, J = 6.75 Hz, 6 H, CH3), 3.04 (q, J = 6.75 Hz, 4 H, CH2),
9.25 (br s, 1 H, NOH). 13C NMR (CDCl3): δ = 10.80 (CH3), 41.93
(CH2).
2-(2-Chlorophenyl)-2-[hydroxy(methyl)amino]cyclohexa-
none (1m)
Light-yellow powder; isolated yield: 1176 mg (91%); mp 206–
208 °C. 1H NMR (CDCl3): δ = 1.55–2.00 (m, 6 H), 2.44–2.63 (m, 5
H), 7.46–7.52 (m, 3 H), 8.14 (d, J = 0.75 Hz, 1 H), 9.53 (br s, 1 H, –
OH), 10.57 (br s, 1 H, –OH). 13C NMR (CDCl3): δ = 21.60 (CH2),
28.29 (CH2), 29.41 (CH3), 38.26 (CH2), 40.19 (CH2), 72.60 (quat
C), 128.50 (CH), 128.67 (CH), 131.76 (CH), 131.89 (CH), 131.96
(quat C), 135.27 (quat C), 205.28 (quat C, C=O).
N,N-Diisobutylhydroxylamine (1d)
Light-brown powder; isolated yield: 675 mg (93%); mp 57–59 °C.
1H NMR (CDCl3): δ = 1.10 (d, J = 6.75 Hz, 12 H, CH3), 2.28 (m, 2
H, –CH–), 2.80 (q, 1J = 12.25 Hz, 2J = 6.50, 4 H, –CH2–), 9.26 (br s,
1 H, NOH). 13C NMR (CDCl3): δ = 20.72 (CH3), 25.24 (=CH–),
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E