Q. Sha, Y. Wei / Tetrahedron xxx (2013) 1e7
5
of N-substituted hydrazones, dialkylidenehydrazines or oximes can
be obtained, respectively, depending on the base and solvent used.
Especially a new process to convert tosylhydrazones or ketones to
oximes in basic conditions was disclosed with CH3NO2 as the pre-
cursor of hydroxylamine.
IR (KBr): 3028, 2991, 1919, 1597, 1454, 1348, 1184, 1167, 955, 814,
768, 660, 571 cmꢁ1. HRMS (ESI): calculated for C23H24N2O2S
[MþH]þ 393.0455, found 393.0458.
4.3.2. N-(1-(4-Chlorophenyl)ethyl)-N0-(1-(4-chlorophenyl)ethyl-
idene)-4-methylbenzenesulfonohydrazide (2b). Yellowsolid: 53.8 mg
(78% yield), mp 124e125 ꢀC. TLC: Rf¼0.12 (PE/EtOAc, 10:1, SiO2).
4. Experimental
4.1. General
1H NMR (500 MHz, CDCl3):
d
¼7.81e7.78 (m, 2H), 7.58 (d, J¼8 Hz,
2H), 7.43e7.41 (m, 2H), 7.24e7.19 (m, 4H), 7.16 (d, J¼7.5 Hz, 2H),
5.23 (q, J¼7 Hz, 1H), 2.44 (s, 3H), 2.25 (s, 3H), 1.19 (d, J¼7 Hz, 3H).
All substrates and reagents were commercially available and
were used without further purification. Petroleum ether (PE) refers
to the fraction boiling in the 60e90 ꢀC range. The progress of the
reactions was monitored by TLC (silica gel, Polygram SILG/UV 254
plates). Column chromatography was performed on Silicycle silica
gel (200e300 mesh). Melting points were obtained using a Yamato
melting point apparatus Model MP-21 and are uncorrected. 1H and
13C NMR spectra were obtained using a Bruker DRX 500 (500 MHz)
spectrometer in CDCl3 or DMSO-d6 with TMS as the internal stan-
dard. IR spectra were recorded on a Shimadzu spectrophotometer
using KBr discs. High-resolution mass spectra were recorded on an
ESI-ion trap mass spectrometer (4800 Plus MALDI TOF/TOF Ana-
lyzer). The known compounds were identified by comparison of
their physical and spectral data with those reported in the
literature.
13C NMR (125 MHz, CDCl3):
d¼178.61, 143.80, 139.16, 137.47,
135.51, 134.83, 133.37, 129.38, 129.23, 128.80, 128.60, 128.41, 128.21,
59.94, 21.63, 17.47, 16.12.
IR (KBr): 3094, 2984, 1919, 1595, 1491, 1398, 1354, 1161, 932, 814,
667, 592 cmꢁ1. HRMS (ESI): calculated for C23H22Cl2N2O2S [MþH]þ
460.9579, found 460.9585.
4.3.3. N-(1-(4-Methoxyphenyl)ethyl)-N0-(1-(4-methoxyphenyl)eth-
ylidene)-4-methylbenzenesulfonohydrazide (2c). Colorless liquid:
55.6 mg (82% yield). TLC: Rf¼0.13 (PE/EtOAc, 10:1, SiO2).
1H NMR (500 MHz, CDCl3):
d
¼7.81 (d, J¼9 Hz, 2H), 7.63 (d,
J¼7.5 Hz, 2H), 7.21 (d, J¼7.5 Hz, 2H), 7.17 (d, J¼8.5 Hz, 2H), 6.92 (d,
J¼9 Hz, 2H), 6.70 (d, J¼7.5 Hz, 2H), 5.23 (q, J¼7 Hz, 1H), 3.85 (s, 3H),
3.74 (s, 3H), 2.41 (s, 3H), 2.12 (s, 3H), 1.15 (d, J¼7 Hz, 3H).
13C NMR (125 MHz, CDCl3):
d
¼178.59, 162.00, 158.88, 143.26,
135.36, 129.87, 129.24, 129.08, 129.04, 128.54, 113.73, 113.33, 59.97,
55.43, 55.23, 21.61, 17.02.
4.2. Typical procedure
IR (KBr): 2933, 2559, 2060, 1892, 1736, 1599, 1512, 1346, 1252,
4.2.1. Metal free NeH insertion reactions of tosylhydrazones (1a as
an example). A Schlenk tube with a magnetic stir bar charged with
hydrazone 1a (0.3 mmol), K2CO3 (0.3 mmol), and CH3NO2 (3 mL).
The system was heated at 90 ꢀC with stirring for 3 h. The reaction
mixture was then allowed to cool to ambient temperature. After
concentrated in vacuo, the crude product was purified by column
chromatography.
1161, 1030, 962, 835, 658, 555 cmꢁ1. HRMS (ESI): calculated for
C
25H28N2O4S [MþH]þ 453.0550, found 453.0533.
4.3.4. N-(1-(3-Methoxyphenyl)ethyl)-N0-(1-(3-methoxyphenyl)eth-
ylidene)-4-methylbenzenesulfonohydrazide
(2d). White
solid:
58.3 mg (86% yield), mp 55e56 ꢀC. TLC: Rf¼0.16 (PE/EtOAc,10:1, SiO2).
1H NMR (500 MHz, CDCl3):
d
¼7.65 (d, J¼6 Hz, 2H), 7.44e7.41 (m,
2H), 7.35 (t, J¼8 Hz, 1H), 7.22 (d, J¼6 Hz, 2H), 7.12 (m, 1H), 7.04 (d,
J¼6.5 Hz, 1H), 6.88e6.86 (m, 2H), 6.74 (d, J¼6.5 Hz, 1H), 5.24 (q,
J¼6 Hz, 1H), 3.86 (s, 3H), 3.70 (s, 3H), 2.42 (s, 3H), 2.24 (s, 3H), 1.21
(d, J¼5.5 Hz, 3H).
4.2.2. The reactions of tosylhydrazones toward oximes (1a as an
example). A Schlenk tube with a magnetic stir bar charged with
hydrazone 1a (0.3 mmol), NaOH (3 mmol), CH3NO2 (1.5 mL), and
DMSO (1.5 mL). The system was heated at 110 ꢀC with stirring for
16 h, The reaction mixture was then allowed to cool to ambient
temperature, and diluted with 20 mL of ethyl acetate, and washed
with brine (30 mL), water (30 mL), and then the organic layer was
dried over Na2SO4. After concentrated in vacuo, the crude product
was purified by column chromatography.
13C NMR (125 MHz, CDCl3):
d¼179.48, 159.55, 159.35, 143.49,
142.38, 138.80, 135.05, 129.47, 129.11, 129.05, 128.55, 120.42, 119.97,
116.53, 113.42, 113.24, 112.72, 60.65, 55.34, 55.11, 21.62, 17.69, 16.15.
IR (KBr): 2935, 2351,1921,1601,1487,1348,1286,1161,1045, 876,
787, 660, 567 cmꢁ1. HRMS (ESI): calculated for C25H28N2O4S
[MþH]þ 453.0550, found 453.0560.
4.2.3. The reactions of tosylhydrazones toward dialkylidenehy-
drazines (1a as an example). A Schlenk tube with a magnetic stir
bar charged with hydrazone 1a (0.3 mmol), CH3NO2 (1.5 mmol),
NaOH (0.9 mmol), and Dioxane (3 mL). The system was heated at
110 ꢀC with stirring for 10 h. The reaction mixture was then allowed
to cool to ambient temperature. After concentrated in vacuo, the
crude product was purified by column chromatography.
4.3.5. N-(1-(2,4-Dichlorophenyl)ethyl)-N0-(1-(2,4-dichlorophenyl)
ethylidene)-4-methylbenzenesulfonohydrazide (2e). White solid:
64.2 mg (81% yield), mp 161e162 ꢀC. TLC: Rf¼0.79 (PE/EtOAc, 3:1, SiO2).
1H NMR (500 MHz, CDCl3):
d¼7.63 (d, J¼8 Hz, 2H), 7.45 (d,
J¼2 Hz, 1H), 7.37e7.32 (m, 3H), 7.26 (d, J¼8.5 Hz, 1H), 7.18 (d,
J¼7.5 Hz, 2H), 6.97 (d, J¼7.5 Hz, 1H), 5.68 (q, J¼7 Hz, 1H), 2.39 (s,
3H), 2.33 (s, 3H), 1.29 (d, J¼7 Hz, 3H).
13C NMR (125 MHz, CDCl3):
135.84, 134.51, 134.04, 133.72, 132.10, 130.19, 129.92, 129.86, 129.33,
129.09, 128.48, 127.48, 126.86, 56.01, 21.76, 21.58, 17.82.
d
¼182.76, 144.01, 137.16, 136.99,
4.3. Characterization data
4.3.1. 4-Methyl-N-(1-phenylethyl)-N0-(1-phenylethylidene)benzene-
sulfonohydrazide (2a). White solid: 56.4 mg (96% yield), mp
166e168 ꢀC. TLC: Rf¼0.36 (PE/EtOAc, 10:1, SiO2).
IR (KBr): 3065, 2976, 1913, 1637, 1591, 1475, 1346, 1167, 1099,
1043, 866, 822, 663, 582 cmꢁ1
. HRMS (ESI): calculated for
C
23H20Cl4N2O2S [MþH]þ 528.8832, found 528.8841.
1H NMR (500 MHz, CDCl3):
d
¼7.82 (d, J¼7.5 Hz, 2H), 7.66 (d,
J¼8 Hz, 2H), 7.48 (t, J¼8 Hz, 3H), 7.42 (t, J¼7.5 Hz, 3H), 7.27e7.21 (m,
4H), 7.20e7.18 (m, 3H), 5.27 (q, J¼7 Hz,1H), 2.42 (s, 3H), 2.14 (s, 3H),
1.20 (d, J¼7 Hz, 3H).
4.3.6. N-(4-(Dimethylamino)benzyl)-N0-(4-(dimethylamino)benzyli-
dene)-4-methylbenzenesulfonohydrazide (2f). Pink solid: 60.7 mg
(90% yield), mp 127e129 ꢀC. TLC: Rf¼0.44 (PE/EtOAc, 10:1, SiO2).
13C NMR (125 MHz, CDCl3):
d
¼179.71, 143.49, 140.89, 137.42,
1H NMR (500 MHz, CDCl3):
7.46 (d, J¼8.5 Hz, 2H), 7.33 (d, J¼8 Hz, 2H), 7.19 (d, J¼7 Hz, 2H),
6.67e6.62 (m, 4H), 4.50 (s, 2H), 3.00 (s, 6H), 2.92 (s, 6H), 2.44 (s, 3H).
d
¼2.87 (s, 1H), 7.81 (d, J¼8 Hz, 2H),
135.23, 131.00, 129.22, 128.54, 128.45, 128.13, 128.07, 127.46, 127.33,
60.55, 21.63, 17.47, 15.47.