N-Alkylation of tosylhydrazones in the presence of triphenylphosphine

Article abstract of DOI:10.1016/j.tet.2013.05.131

An efficient N-alkylation reaction of tosylhydrazones was developed in the presence of triphenylphosphine; triphenylphosphine played a key role in the transformation. A range of N-alkylated tosylhydrazones were prepared in good to high yields.

Full text of DOI:10.1016/j.tet.2013.05.131

Tetrahedron 69 (2013) 7487e7491
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
N-Alkylation of tosylhydrazones in the presence
of triphenylphosphine
*
Yuanfang Kong, Wen Zhang, Meng Tang , Haiming Wang
School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient N-alkylation reaction of tosylhydrazones was developed in the presence of triphenylphos-
phine; triphenylphosphine played a key role in the transformation. A range of N-alkylated tosylhy-
drazones were prepared in good to high yields.
Received 20 March 2013
Received in revised form 23 May 2013
Accepted 30 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Available online 5 June 2013
Keywords:
N-Alkylation
Tosylhydrazones
Triphenylphosphine
1. Introduction
alkylation of tosylhydrazones using an alkyl halide/base in the
presence of a phase-transfer catalyst.5 In order to prevent the
Tosylhydrazones are versatile synthetic intermediates capable
of acting as both nucleophiles and electrophiles.1,5 It is well
known that under basic conditions tosylhydrazones form non-
stabilized diazo compounds through a BamfordeStevens reaction
(Scheme 1a), and they have been used as in situ sources of diazo
compounds in different types of metal-catalyzed and metal-free
reactions.2,3
competitive decomposition of tosylhydrazones, Cacchi et al. carried
out the reaction at room temperature in a two-phase system;
a large excess of alkyl halide (1.5e4.0 equiv) and a phase-transfer
catalyst were essential. Recently, N-alkylation of tosylhydrazones
has been achieved using alcohols under Mitsunobu6 or acid-
catalyzed reaction conditons;7 a reductive coupling procedure has
also been reported.8,9
2. Results and discussion
In the course of our study of the reactions of tosylhy-
drazones,10 we found that when treated with 1.5 equiv of K2CO3
at reflux temperature, tosylhydrazone (1a) disappeared within
3 h (Scheme 1a), but in the presence of 0.1 equiv of triphenyl-
phosphine, this process required more than 5 h (Scheme 1b),
and if 1.0 equiv of triphenylphosphine was used, the process can
be extended to more than 12 h (Scheme 1c). This shows that
triphenylphosphine can be used as a stabilizer in this process.
A careful literature survey revealed that this phenomenon has
not been reported previously. We decided to use triphenyl-
phosphine as a stabilizer in exploring the basic chemistry
of tosylhydrazones. First, we investigated the N-alkylation
reactions of tosylhydrazones with halides in the presence of
triphenylphosphine.
Scheme 1.
N-Alkylated hydrazones are useful synthons and have various
applications in organic synthesis.4 Cacchi et al. reported an N-
We used tosylhydrazone (1a) as a model substrate, and screened
the reaction conditions (Table 1). As shown by the data in Table 1,
when K2CO3 was used as the base, triphenylphosphine significantly
* Corresponding author. E-mail address: tangmeng@lzu.edu.cn (M. Tang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.131

7488
Y. Kong et al. / Tetrahedron 69 (2013) 7487e7491
Table 1
4. Experimental section
Screening the reaction conditions
4.1. General remarks
For product purification by flash column chromatography, silica
gel (200e300 mesh) and light petroleum ether (bp 60e90 ꢀC) are
used. All organic extracts were dried over anhydrous MgSO4. 1H and
13C NMR spectra were taken on a Varian Mercury-400 MHz spec-
trometer with TMS as an internal standard and CDCl3 as solvent.
The HRMS data were determined on a Bruker Daltonics APEXII 47e
FT-ICR spectrometer.
Entry
Sol
Base
PPh3 (equiv)
Temp
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
Benzene
CH2Cl2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
NaHCO3
Cs2CO3
NaOH
NaOMe
NaH
0
rt
rt
rt
rt
rt
rt
rt
Reflux
rt
rt
rt
rt
rt
rt
rt
rt
rt
36
36
36
36
36
45
45
1.5
96
96
28
96
96
36
80
25
26
41
95
97
99
91
89
85
86
10
Trace
92
68
53
53
89
77
94
0.1
0.2
0.3
0.4
0.5
1.0
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
4.2. General procedure for the preparation of tosylhy-
drazones (1aeg)
9
Tosylhydrazones (1aeg) were prepared from TsNHNH2 and
corresponding aldehydes or ketones by the known procedure.12 To
a rapidly stirred suspension of TsNHNH2 (1.05 equiv) in methanol
was added aldehyde or ketone (1.0 equiv) dropwise (solid reagents
were added portion-wise). A mildly exothermic reaction ensued
and the hydrazide dissolved. Within 5e10 min the tosylhydrazone
began to precipitate. After approximately 30 min, the mixture was
cooled to 0 ꢀC and the product was collected by filtration, washed
with cooled methanol. All of the obtained solids could be recrys-
tallized from methanol or used without further purification.
10
11
12
13
14
15
16
17
K2CO3
K2CO3
K2CO3
a
The yields are for the isolated product.
improved the yield of the desired product 2a (entries 1e8, Table 1),
and 0.3 equiv of triphenylphosphine gave the best result (entry 4,
Table 1).
4.3. Typical representative procedure for the synthesis N-
benzyl-N0-benzylidene-4-methylbenzenesulfonohydrazide
(2a)
Increasing the amount of triphenylphosphine slightly reduced
the yield (entries 5e7, Table 1). This may be because the formation
of a phosphonium salt between triphenylphosphine and benzyl
bromide affects the N-alkylation reaction.11 The reaction can be
carried out at reflux temperature, but the yield is lower (entry 8,
Table 1). Of the bases screened, weaker alkalis gave disappointing
results (entries 9 and 10, Table 1). Cs2CO3 gave a similar yield
(entry 11, Table 1), and the yield was reduced when NaOH, NaOMe
or NaH was used (entries 12e14, Table 1). It was observed that the
reaction proceeded smoothly in various solvents, such as Et2O,
benzene, and CH2Cl2 (entries 15e17, Table 1), giving 2a in good to
high yields.
Under the optimized conditions, the syntheses of various N-
alkylated tosylhydrazones were attempted, to investigate the scope
of the method. As shown in Table 2, an aliphatic aldehyde tosyl-
hydrazone (1e), a range of aromatic aldehyde tosylhydrazones (1a,
1d, and 1g) and aliphatic ketone tosylhydrazones (1c and 1f), and
an aromatic ketone tosylhydrazone (1b) could be used, and affor-
ded the corresponding products in good to high yields. In addition
to benzyl bromide, methyl iodide and allyl bromide also gave good
yields.
Under argon atmosphere, K2CO3 (38 mg, 0.28 mmol) was
added to a mixture of 1a (50 mg, 0.18 mmol), PPh3 (14 mg,
0.05 mmol), and benzyl bromide (34 mg, 0.20 mmol) in THF
(3 mL), the mixture was stirred at room temperature for 36 h. The
product was extracted with Et2O and the organic layer was
washed with brine, dried over anhydrous MgSO4, filtered, and
concentrated in vacuo. Purification by chromatography on silica
gel afforded the desired product 2a as white crystalline solid
(66 mg, 99%). Mp 112e114 ꢀC; dH (400 MHz, CDCl3) 2.42 (3H, s),
4.85 (2H, s), 7.25e7.28 (1H, m), 7.32e7.34 (9H, m), 7.50e7.52 (2H,
m), 7.58 (1H, s), 7.87 (2H, d, J 8.4 Hz); dC (100 MHz, CDCl3) 21.5,
51.9, 126.8, 127.3, 127.6, 128.2, 128.5, 128.8, 129.5, 130.0, 133.9,
134.5, 135.3, 144.0, 146.5; HRMS (ESI): MHþ, found: 365.1313.
C21H21N2O2S requires 365.1318.
4.3.1. Preparation of N-methyl-N0-benzylidene-4-methylben
zenesulfonohydrazide (2b). Compound 2b (52 mg, 99%) was pre-
pared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1a (50 mg, 0.18 mmol), PPh3 (14 mg,
0.05 mmol), and iodomethane (29 mg, 0.20 mmol) as white crys-
talline solid. Mp 99e101 ꢀC; dH (400 MHz, CDCl3) 2.38 (3H, s), 3.22
(3H, s), 7.26e7.30 (2H, m), 7.36e7.37 (3H, m), 7.57 (1H, s), 7.63e7.65
(2H, m), 7.79 (2H, d, J 8.0 Hz); dC (100 MHz, CDCl3) 21.5, 33.3, 127.2,
128.1, 128.6, 129.5, 129.9, 133.4, 134.1, 143.6, 144.0; HRMS (ESI):
MHþ, found: 289.1008. C15H17N2O2S requires 289.1005.
Although there is not yet sufficient evidence to confirm the re-
action mechanism, it is indisputable that triphenylphosphine
played a key role in the transformations. We performed compara-
tive experiments, without using triphenylphosphine, for each ex-
ample. It was particularly significant that lower yields were
obtained in the absence of triphenylphosphine in all of the com-
parative experiments (entries 1e20, Table 2).
4.3.2. Preparation of N-allyl-N0-benzylidene-4-methylben
zenesulfonohydrazide (2c). Compound 2c (57 mg, 99%) was pre-
pared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1a (50 mg, 0.18 mmol), PPh3 (14 mg,
0.05 mmol), and allyl bromide (24 mg, 0.20 mmol) as yellow
crystalline solid. Mp 74e76 ꢀC; dH (400 MHz, CDCl3) 2.40 (3H, s),
4.36 (2H, d, J 3.6 Hz), 5.20e5.28 (2H, m), 5.75e5.82 (1H, m), 7.29
(2H, d, J 8.0 Hz), 7.35e7.36 (3H, m), 7.60e7.61 (2H, m), 7.69 (1H, s),
7.83 (2H, d, J 8.0 Hz); dC (100 MHz, CDCl3) 21.5, 49.8, 118.1, 127.2,
3. Conclusions
In conclusion, we have developed an N-alkylation of tosylhy-
drazones in the presence of triphenylphosphine. The reaction
conditions were mild and efficient, and provided the products in
good to high yields. Further studies on the reaction mechanism are
underway in our laboratory.

Y. Kong et al. / Tetrahedron 69 (2013) 7487e7491
7489
Table 2
N-Alkylation of tosylhydrazones in the presence of triphenylphosphine
Entry
1
Substrate 1
R3eX
Time (h)
46
Product 2
Yielda (%)
99 (82)
Entry
11
Substrate 1
R3eX
Time (h)
48
Product
Yielda (%)
1a
CH3I
84 (51)
2
3
1a
26
96
99 (16)
92 (34)
12
13
1e
1e
CH3I
46
35
79 (72)
90 (35)
4
5
6
7
1b
1b
CH3I
84
45
96
48
95 (44)
99 (28)
97 (39)
89 (21)
14
15
16
17
90
26
40
26
85 (70)
76 (22)
89 (11)
88 (52)
1f
1f
CH3I
1c
8
9
15
18
28
95 (8)
99 (82)
99 (7)
18
19
20
1g
1g
CH3I
30
20
12
97 (86)
99 (21)
97 (67)
1d
1d
CH3I
10
CH3I
a
The yields in parentheses are the results of without use of triphenylphosphine.

7490
Y. Kong et al. / Tetrahedron 69 (2013) 7487e7491
128.1, 128.5, 129.4, 130.0, 131.1, 134.0, 134.7, 143.9, 145.4; HRMS
(ESI): MHþ, found: 315.1158. C17H19N2O2S requires 315.1162.
129.6, 134.0, 135.2, 139.7, 144.2, 144.5, 149.2; HRMS (ESI): MHþ,
found 355.1107. C19H19N2O3S requires 355.1111.
4.3.9. Preparation of N-methyl-N0-(furan-20-ylmethylene)-4-methyl
benzenesulfonohydrazide (2j). Compound 2j (50 mg, 99%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1d (48 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and iodomethane (28 mg, 0.20 mmol) as yellow oil. dH
(400 MHz, CDCl3) 2.40 (3H, s), 3.15 (3H, s), 6.46 (1H, d, J 1.2 Hz), 6.71
(1H, d, J 3.2 Hz), 7.29 (2H, d, J 8.4 Hz), 7.49 (1H, s), 7.55 (1H, s), 7.77
(2H, d, J 8.4 Hz); dC (100 MHz, CDCl3) 21.5, 33.9, 111.7, 112.4, 128.2,
129.4, 133.0, 135.4, 144.1, 144.3, 149.6; HRMS (ESI): MHþ, found:
279.0802. C13H15N2O3S requires 279.0798.
4.3.3. Preparation of N-benzyl-N0-(10-phenylethylidene)-4-methy
lbenzenesulfonohydrazide (2d). Compound 2d (64 mg, 92%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol),1b (53 mg, 0.18 mmol), PPh3 (14 mg, 0.05 mmol),
and benzyl bromide (35 mg, 0.20 mmol) as white crystalline solid.
Mp 116e120 ꢀC; dH (400 MHz, CDCl3) 2.17 (3H, s), 2.48 (3H, s), 4.25
(2H, s), 7.23e7.25 (5H, m), 7.34e7.43 (5H, m), 7.66 (2H, d, J 7.2 Hz),
7.78 (2H, d, J 8.0 Hz); dC (100 MHz, CDCl3) 17.8, 21.6, 56.6, 127.1, 127.7,
128.2, 129.1, 129.4,129.7, 130.8,132.0,135.4,137.1, 144.1, 178.3; HRMS
(ESI): MHþ, found: 379.1479. C22H23N2O2S requires 379.1475.
4.3.10. Preparation of N-allyl-N0-(furan-20-ylmethylene)-4-methyl
benzenesulfonohydrazide (2k). Compound 2k (55 mg, 99%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1d (48 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and allyl bromide (34 mg, 0.20 mmol) as yellow crys-
talline solid. Mp 96e98 ꢀC; dH (400 MHz, CDCl3) 2.41 (3H, s), 4.23
(2H, d, J 4.4 Hz), 5.19e5.27 (2H, m), 5.73e5.79 (1H, m), 6.46 (1H, dd, J
3.2, 1.6 Hz), 6.71 (1H, d, J 3.2 Hz), 7.31 (2H, d, J 8.0 Hz), 7.49 (1H, s),
7.78(1H, s), 7.79 (2H, d, J 8 Hz); dC (100 MHz, CDCl3) 21.5, 50.8, 111.8,
113.2,118.3,128.2,129.5,131.2,134.2,138.8,144.1,144.5,149.4; HRMS
(ESI): MHþ, found: 305.0959. C15H17N2O3S requires 305.0954.
4.3.4. Preparation of N-methyl-N0-(10-phenylethylidene)-4-methy
lbenzenesulfonohydrazide (2e). Compound 2e (53 mg, 95%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol),1b (53 mg, 0.18 mmol), PPh3 (14 mg, 0.05 mmol),
and iodomethane (29 mg, 0.20 mmol) as white crystalline solid. Mp
128e130 ꢀC; dH (400 MHz, CDCl3) 2.45 (3H, s), 2.57 (3H, s), 2.81 (3H,
s), 7.36e7.46 (5H, m), 7.77e7.80 (4H, m); dC (100 MHz, CDCl3) 16.8,
21.5, 39.2, 127.0, 128.3, 129.2, 129.4, 130.8, 137.0, 144.0, 174.2; HRMS
(ESI): MHþ, found 303.1166. C16H19N2O2S requires 303.1162.
4.3.5. Preparation of N-allyl-N0-(10-phenylethylidene)-4-methy
lbenzenesulfonohydrazide (2f). Compound 2f (60 mg, 99%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1b (53 mg, 0.18 mmol), PPh3 (14 mg,
0.05 mmol), and allyl bromide (24 mg, 0.20 mmol) as colorless oil.
dH (400 MHz, CDCl3) 2.45 (3H, s), 2.59 (3H, s), 3.76 (2H, d, J 6.4 Hz),
5.04e5.11 (2H, m), 5.68e5.72 (1H, m), 7.34e7.48 (5H, m), 7.72 (2H,
d, J 8.0 Hz), 7.79 (2H, d, J 7.2 Hz); dC (100 MHz, CDCl3) 18.1, 21.6, 55.4,
119.5, 127.1, 128.4, 129.0, 129.2, 129.4, 130.9, 132.1, 137.2, 144.1, 177.7;
HRMS (ESI): MHþ, found: 329.1322. C18H21N2O2S requires 329.1318.
4.3.11. Preparation of N-benzyl-N0-(30-phenylpropylidene)-4-methyl
benzenesulfonohydrazide (2l). Compound 2l (83 mg, 84%) was
prepared following the procedure described for 2a by using K2CO3
(52 mg, 0.38 mmol), 1e (76 mg, 0.25 mmol), PPh3 (20 mg,
0.08 mmol), and benzyl bromide (47 mg, 0.27 mmol) as yellow
crystalline solid. Mp 88e90 ꢀC; dH (400 MHz, CDCl3) 2.44 (3H, s),
2.45e2.51 (2H, m), 2.68 (2H, t, J 7.6 Hz), 4.54 (2H, s), 6.98 (2H, d, J
7.6 Hz), 7.12e7.32 (11H, m), 7.74 (2H, d, J 8.0 Hz); dC (100 MHz,
CDCl3) 21.6, 32.2, 34.3, 52.6, 126.0, 127.2, 127.5, 128.2, 128.7, 129.5,
134.0, 135.4, 140.4, 143.9, 155.1; HRMS (ESI): MHþ, found: 393.1626.
4.3.6. Preparation of N-benzyl-N0-(propan-20-ylidene)-4-methyl
benzenesulfonohydrazide (2g). Compound 2g (77 mg, 97%) was
prepared following the procedure described for 2a by using K2CO3
(52 mg, 0.38 mmol), 1c (57 mg, 0.25 mmol), PPh3 (20 mg,
0.08 mmol), and benzyl bromide (47 mg, 0.27 mmol) as white
crystalline solid. Mp 127e129 ꢀC; dH (400 MHz, CDCl3) 1.78 (3H, s),
1.92 (3H, s), 2.46 (3H, s), 4.12 (2H, s), 7.24e7.26 (5H, m), 7.37 (2H, d, J
7.6 Hz), 7.74 (2H, d, 8.4 Hz); dC (100 MHz, CDCl3) 20.7, 21.6, 24.8,
56.1, 127.6, 128.2, 128.9, 129.39, 129.44, 129.6, 132.1, 135.5, 144.0;
HRMS (ESI): MHþ, found: 317.1322. C17H21N2O2S requires 317.1318.
C
23H25N2O2S requires 393.1631.
4.3.12. Preparation of N-methyl-N0-(30-phenylpropylidene)-4-methyl
benzenesulfonohydrazide (2m). Compound 2m (63 mg, 79%) was
prepared following the procedure described for 2a by using K2CO3
(52 mg, 0.38 mmol), 1e (76 mg, 0.25 mmol), PPh3 (20 mg,
0.08 mmol), and iodomethane (39 mg, 0.27 mmol) as colorless oil.
dH (400 MHz, CDCl3) 2.42 (3H, s), 2.59e2.64 (2H, m), 2.81 (2H, t, J
7.6 Hz), 2.98 (3H, s), 7.05 (1H, t, J 4.4 Hz), 7.12 (2H, d, J 6.8 Hz), 7.19
(1H, d, J 6.8 Hz), 7.23e7.28 (4H, m), 7.68 (2H, d, J 8.0 Hz); dC
(100 MHz, CDCl3) 21.5, 32.5, 33.7, 34.2, 126.0, 128.3, 128.4, 129.3,
132.8, 140.5, 143.8, 149.1; HRMS (ESI): MHþ, found: 317.1322.
4.3.7. Preparation of N-allyl-N0-(propan-20-ylidene) -4-methyl
benzenesulfonohydrazide (2h). Compound 2h (44 mg, 89%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1c (42 mg, 0.19 mmol), PPh3 (15 mg,
0.06 mmol), and allyl bromide (25 mg, 0.21 mmol) as colorless oil.
dH (400 MHz, CDCl3) 2.08 (3H, s), 2.19 (3H, s), 2.43 (3H, s), 3.62 (2H,
d, J 6.0 Hz), 5.06e5.11 (2H, m), 5.63e5.70 (1H, m), 7.33 (2H, d, J
8.0 Hz), 7.68 (2H, d, J 8.0 Hz); dC (100 MHz, CDCl3) 21.1, 21.5, 25.0,
54.9, 119.4, 128.9, 129.3, 131.8, 132.2, 144.0, 181.3; HRMS (ESI): MHþ,
found: 267.1165. C13H19N2O2S requires 267.1162.
C17H21N2O2S requires 317.1318.
4.3.13. Preparation of N-allyl-N0-(30-phenylpropylidene)-4-
methylbenzenesulfonohydrazide (2n). Compound 2n (56 mg, 90%)
was prepared following the procedure described for 2a by using
K2CO3 (38 mg, 0.28 mmol), 1e (55 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and allyl bromide (24 mg, 0.20 mmol) as yellow oil. dH
(400 MHz, CDCl3) 2.42 (3H, s), 2.58e2.63 (2H, m), 2.82 (2H, t, J
7.6 Hz), 4.04 (2H, d, J 4.4 Hz), 5.12 (2H, d, J 12.4 Hz), 5.64 (1H, dt, J
17.2, 5.2 Hz), 7.13 (2H, d, J 7.2 Hz), 7.19 (1H, d, J 6.8 Hz), 7.23e7.28
(5H, m), 7.69 (2H, d, 8.4 Hz); dC (100 MHz, CDCl3) 21.5, 32.3, 34.3,
50.7, 118.1, 126.1, 128.2, 128.4, 129.4, 131.5, 134.1, 140.5, 143.8, 154.0;
HRMS (ESI): MHþ, found: 343.1471. C19H23N2O2S requires 343.1475.
4.3.8. Preparation of N-benzyl-N0-(furan-20-ylmethylene)-4-methyl
benzenesulfonohydrazide (2i). Compound 2i (61 mg, 95%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1d (48 mg, 0.18 mmol), PPh3 (15 mg,
0.09 mmol), and benzyl bromide (34 mg, 0.20 mmol) as white
crystalline solid. Mp 120e122 ꢀC; dH (400 MHz, CDCl3) 2.42 (3H, s),
4.73 (2H, s), 6.40 (1H, s), 6.61 (1H, d, J 3.6 Hz), 7.24e7.27 (1H, m),
7.31e7.34 (6H, m), 7.43 (1H, s), 7.62 (1H, s), 7.83 (2H, d, J 8.0 Hz); dC
(100 MHz, CDCl3) 21.5, 52.7, 111.7, 113.5, 127.1, 127.6, 128.2, 128.8,
4.3.14. Preparation of N-benzyl-N0-cyclohexylidene-4-methylben
zenesulfonohydrazide (2o). Compound 2o (56 mg, 85%) was pre-
pared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol),1f (49 mg, 0.18 mmol), PPh3 (15 mg, 0.06 mmol),
and benzyl bromide (35 mg, 0.20 mmol) as white crystalline solid.

Y. Kong et al. / Tetrahedron 69 (2013) 7487e7491
7491
Mp 148e151 ꢀC; dH (400 MHz, CDCl3) 1.06 (2H, s), 1.42 (2H, d, J
4.8 Hz),1.51 (2H, d, J 4.8 Hz), 2.22 (2H, t, J 6.0 Hz), 2.37 (2H, t, J 6.0 Hz),
2.45 (3H, s), 4.14 (2H, s), 7.25 (5H, s), 7.36 (2H, d, J 8.0 Hz), 7.74 (2H, d, J
8.0 Hz); dC (100 MHz, CDCl3) 21.6, 25.4, 26.0, 27.3, 31.0, 35.7, 55.8,
127.6, 128.1, 128.9, 129.4, 129.8, 132.2, 135.4, 143.9, 186.6; HRMS
(ESI): MHþ, found: 357.1627. C20H25N2O2S requires 357.1631.
following the procedure described for 2a by using K2CO3 (52 mg,
0.38 mmol), 1h (80 mg, 0.25 mmol), PPh3 (20 mg, 0.08 mmol), and
iodomethane (39 mg, 0.27 mmol) as yellow crystalline solid. Mp
169e171 ꢀC; dH (400 MHz, CDCl3) 2.41(3H, s), 3.31 (3H, s), 7.32 (2H,
d, J 8.0 Hz), 7.53 (1H, s), 7.79 (4H, t, J 8.0 Hz), 8.22 (2H, d, J 8.4 Hz); dC
(100 MHz, CDCl3) 21.5, 32.9, 123.9, 127.5, 127.9, 129.7, 133.5, 138.6,
140.2, 144.5, 148.1; HRMS (ESI): MHþ, found 334.0851. C15H16N3O4S
requires 334.0856.
4.3.15. Preparation of N-methyl-N0-cyclohexylidene-4-methyl
benzenesulfonohydrazide (2p). Compound 2p (39 mg, 76%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1f (49 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and iodomethane (29 mg, 0.20 mmol) as yellow oil. dH
(400 MHz, CDCl3) 1.65e1.66 (2H, m), 1.74e1.76 (4H, m), 2.34 (2H, t, J
6.0 Hz), 2.43 (3H, s), 2.71e2.74 (5H, m), 7.33 (2H, d, J 8.0 Hz), 7.70
(2H, d, J 8.0 Hz); dC (100 MHz, CDCl3) 21.5, 25.6, 26.6, 27.3, 30.2, 35.8,
39.2, 129.3, 130.8, 143.9, 183.4; HRMS (ESI): MHþ, found: 281.1315.
Acknowledgements
We are grateful for financial support from NSFC (No. 21002044)
and the Fundamental Research Funds for the Central Universities
(lzujbky-2012-89).
Supplementary data
C
14H21N2O2S requires 281.1318.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.05.131.
4.3.16. Preparation of N-allyl-N0-cyclohexylidene-4-methyl
benzenesulfonohydrazide (2q). Compound 2q (50 mg, 89%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1f (49 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and allyl bromide (25 mg, 0.21 mmol) as colorless oil.
dH (400 MHz, CDCl3) 1.64e1.74 (6H, m), 2.35 (2H, t, J 6.0 Hz), 2.43
(3H, s), 2.73 (2H, t, J 6.0 Hz), 3.63 (2H, d, J 6.0 Hz), 5.07e5.11 (2H, m),
5.63e5.69 (1H, m), 7.32 (2H, d, J 8.0 Hz), 7.67 (2H, d, J 8.0 Hz); dC
(100 MHz, CDCl3) 21.5, 25.7, 26.6, 27.6, 31.1, 35.9, 54.6, 119.3, 128.9,
129.3, 131.9, 132.4, 143.9, 186.2; HRMS (ESI): MHþ, found 307.1470.
References and notes
1. (a) Hashemi, S. A. Tetrahedron Lett. 2012, 53, 5141e5143; (b) Zhao, G.-L.; Shi, M.
Tetrahedron 2005, 61, 7277e7288; (c) Keith, J. M.; Jacobsen, E. N. Org. Lett. 2004,
6, 153e155; (d) Ogawa, C.; Konishi, H.; Sugiura, M.; Kobayashi, S. Org. Biomol.
Chem. 2004, 2, 446e448.
2. For selected reviews, see: (a) Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res.
2013, 46, 236e247; (b) Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org.
Chem. 2005, 1479e1492; (c) Zhang, Y.; Wang, J. Top. Curr. Chem. 2012, 327,
239e270; (d) Shao, Z.; Zhang, H. Chem. Soc. Rev. 2012, 41, 560e572; (e)
C
16H23N2O2S requires 307.1475.
ꢀ
Barluenga, J.; Valdes, C. Angew. Chem., Int. Ed. 2011, 50, 7486e7500.
3. For selected recently examples on the reactions of N-tosylhydrazones, see: (a)
Ojha, D. P.; Prabhu, K. R. J. Org. Chem. 2012, 77, 11027e11033; (b) Roche, M.;
Hamze, A.; Provot, O.; Brion, J.-D.; Alami, M. J. Org. Chem. 2013, 78, 445e454; (c)
Xia, Y.; Qu, P.; Liu, Z.; Ge, R.; Xiao, Q.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed.
2013, 52, 2543e2546; (d) Hossain, M. L.; Ye, F.; Zhang, Y.; Wang, J. J. Org. Chem.
2013, 78, 1236e1241; (e) Xiao, Q.; Ling, L.; Ye, F.; Tan, R.; Tian, L.; Zhang, Y.; Li,
Y.; Wang, J. J. Org. Chem. 2013, 78, 3879e3885.
4. (a) Mundal, D. A.; Lutz, K. E.; Thomson, R. J. Org. Lett. 2009, 11, 465e468; (b) Lee,
Y. T.; Chung, Y. K. J. Org. Chem. 2008, 73, 4698e4701; (c) Movassaghi, M.;
Ahmed, O. K. Angew. Chem., Int. Ed. 2008, 47, 8909e8912; (d) Movassaghi, M.;
Ahmad, O. K. J. Org. Chem. 2007, 72, 1838e1841; (e) Benstead, D. J.; Hulme, A. N.;
McNab, H.; Wight, P. Synlett 2005, 1571e1574; (f) Kobayashi, S.; Hirabayashi, R.
J. Am. Chem. Soc. 1999, 121, 6942e6943; (g) Myers, A. G.; Movassaghi, M.; Zheng,
B. J. Am. Chem. Soc. 1997, 119, 8572e8573; (h) Myers, A. G.; Zheng, B. J. Am. Chem.
Soc. 1996, 118, 4492e4493; (i) Buchwald, S. L.; Willoughby, C. A. Catalytic
Asymmetric and Nonasymmetric Reduction of Imines and Oximines Using
Metal Catalysts. U.S. Cont.-in-part of U.S. Ser. No. 698940, abandoned, U.S.
5,292,893, 1994. (j) Schantl, J. G.; Hebeisen, P.; Karpellus, P. Synth. Commun.
1989, 19, 39e48.
4.3.17. Preparation of N-benzyl-N0-(40-methoxybenzylidene)-4-meth
ylbenzenesulfonohydrazide (2r). Compound 2r (64 mg, 88%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1g (56 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and benzyl bromide (35 mg, 0.20 mmol) as white
crystalline solid. Mp 110e113 ꢀC; dH (400 MHz, CDCl3) 2.42 (3H, s),
3.79 (3H, s), 4.74 (2H, s), 6.83 (2H, d, J 8.4 Hz), 7.25e7.26 (1H, m),
7.29e7.34 (6H, m), 7.47 (2H, d, J 8.4 Hz), 7.66 (1H, s), 7.83 (2H, d, J
8.0 Hz); dC (100 MHz, CDCl3) 21.5, 52.7, 55.3,113.9,126.5,127.1,127.5,
128.2,128.7,129.1,129.5,134.2,135.7,144.0,149.7,161.3; HRMS (ESI):
MHþ, found: 395.1429. C22H23N2O3S requires 395.1424.
4.3.18. Preparation of N-methyl-N0-(40-methoxybenzylidene)-4-meth
ylbenzenesulfonohydrazide (2s). Compound 2s (77 mg, 97%) was
prepared following the procedure described for 2a by using K2CO3
(52 mg, 0.38 mmol), 1g (76 mg, 0.25 mmol), PPh3 (20 mg,
0.08 mmol), and iodomethane (39 mg, 0.27 mmol) as white crys-
talline solid. Mp 107e109 ꢀC; dH (400 MHz, CDCl3) 2.39 (3H, s), 3.17
(3H, s), 3.83 (3H, s), 6.90 (2H, d, J 8.0 Hz), 7.28 (2H, d, J 7.6 Hz),
7.58e7.61 (3H, m), 7.77 (2H, d, J 8.0 Hz); dC (100 MHz, CDCl3) 21.5,
33.9, 55.3, 114.0, 126.8, 128.2, 128.9, 129.4, 133.2, 143.9, 145.2, 161.1;
HRMS (ESI): MHþ, found 319.1107. C16H19N2O3S requires 319.1111.
5. Cacchi, S.; La Torre, F.; Misiti, D. Synthesis 1977, 301e303.
6. Keith, J. M.; Gomez, L. J. Org. Chem. 2006, 71, 7113e7116.
7. Raji Reddy, C.; Jithender, E. Tetrahedron Lett. 2009, 50, 5633e5635.
8. Liu, J.-B.; Yan, H.; Lu, G. Tetrahedron Lett. 2013, 54, 891e895.
9. For any other examples in preparation of N-alkylated hydrazones, see: (a) He,
R.; Lam, Y. Org. Biomol. Chem. 2008, 6, 2182e2186; (b) Fahey, J. L.; Firestone, R.
A.; Christensen, B. G. J. Med. Chem. 1976, 19, 562e565; (c) Nun, P.; Martin, C.;
Martinez, J.; Lamaty, F. Tetrahedron 2011, 67, 8187e8194.
10. (a) Tang, M.; Zhang, F.-M. Tetrahedron 2013, 69, 1427e1433; (b) Tang, M.; Fan,
C.-A.; Zhang, F.-M.; Tu, Y.-Q.; Zhang, W.-X.; Wang, A.-X. Org. Lett. 2008, 10,
5585e5588.
11. As shown in the following scheme, we have performed experiment using
phosphonium salt 3 instead of triphenylphosphine and benzyl bromide, and the
yield is just 12% after 4 days.
4.3.19. Preparation of N-allyl-N0-(40-methoxybenzylidene)-4-meth-
ylbenzenesulfonohydrazide (2t). Compound 2t (63 mg, 99%) was
prepared following the procedure described for 2a by using K2CO3
(38 mg, 0.28 mmol), 1g (56 mg, 0.18 mmol), PPh3 (15 mg,
0.06 mmol), and allyl bromide (25 mg, 0.21 mmol) as yellow
crystalline solid. Mp 79e81 ꢀC; dH (400 MHz, CDCl3) 2.41 (3H, s),
3.83 (3H, s), 4.25 (2H, d, J 5.2 Hz), 5.18e5.27 (2H, m), 5.74e5.82 (1H,
m), 6.89 (2H, d, J 8.8 Hz), 7.30 (2H, d, J 8.0 Hz), 7.57 (2H, d, J 8.8 Hz),
7.79e7.81 (3H, m); dC (100 MHz, CDCl3) 21.5, 50.7, 55.3, 114.0, 118.1,
126.7, 128.2, 129.1, 129.4, 131.6, 134.4, 143.9, 148.6, 161.3; HRMS
(ESI): MHþ, found: 345.1263. C18H21N2O3S requires 345.1267.
12. Aggarwal, V. K.; Alonso, E.; Bae, I.; Hynd, G.; Lydon, K. M.; Palmer, M. J.; Patel,
M.; Porcelloni, M.; Richardson, J.; Stenson, R. A.; Studley, J. R.; Vasse, J.-L.; Winn,
C. L. J. Am. Chem. Soc. 2003, 125, 10926e10940.
4.3.20. Preparation of N-methyl-N0-(40-nitrobenzylidene)benzene-
sulfonohydrazide (2u). Compound 2u (81 mg, 97%) was prepared