Allylation of N-benzoylhydrazones (=N′-alkylidene-substituted benzohydrazides) by treatment with allyl bromide in the presence of zinc in aqueous ammonium chloride solution

Article abstract of DOI:10.1002/hlca.201100006

N-Benzoylhydrazones (=N′-alkylidene-substituted benzohydrazides) 1 are allylated efficiently by reaction with allyl bromide (2) in the presence of Zn in aqueous NH₄Cl solution. The products 3 are formed in excellent yields (85-94%) within 35-50

Full text of DOI:10.1002/hlca.201100006

Helvetica Chimica Acta – Vol. 94 (2011)
1477
Allylation of N-Benzoylhydrazones (¼ N’-Alkylidene-Substituted
Benzohydrazides) by Treatment with Allyl Bromide in the Presence of Zinc in
Aqueous Ammonium Chloride Solution1)
by Biswanath Das*, Digambar Balaji Shinde, Boddu Shashi Kanth, and Jayprakash Narayan Kumar
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500007, India
(phone: þ 91-40-7193434; fax: þ 91-40-7160512; e-mail: biswanathdas@yahoo.com)
N-Benzoylhydrazones (¼ N’-alkylidene-substituted benzohydrazides) 1 are allylated efficiently by
reaction with allyl bromide (2) in the presence of Zn in aqueous NH4Cl solution. The products 3 are
formed in excellent yields (85 – 94%) within 35 – 50 min (Scheme, Table).
Introduction. – Allylation of imines and related compounds is a valuable organic
transformation as it generates a CꢀC bond and produces homoallylic amine derivatives
of synthetic and biological importance [1]. Significant advances in the Barbier-type
imine allylation have recently been developed [1][2]. However, the methods of
allylation of N-acylhydrazones (¼ N’-alkylidene-substituted hydrazides) are limited
[3], and more importantly, the application of allyl bromide (CH2¼CHCH2Br) has
received only scant attention for this transformation [3f]. Moreover, the use of Zn in
the Barbier-type imine allylation has not been explored much [4]. Here, we report a
simple and convenient method for the allylation of N-benzoylhydrazones (¼ N’-
alkylidene-substituted benzohydrazides) 1 under mild reaction conditions.
Results and Discussion. – In continuation of our work [5] on the development of
useful synthetic methodologies, we have discovered that N-benzoylhydrazones 1 can
undergo allylation efficiently with CH2¼CHCH2Br (2) in the presence of Zn in aqueous
NH4Cl at 08 (Scheme). Various N-benzoylhydrazones 1 derived from different
aldehydes were subjected to the above conversions. The reactions were complete
Scheme
1
)
Part 219 in the series ꢂStudies on Novel Synthetic Methodologiesꢃ.
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 94 (2011)
Table. Allylation of N-Benzoylhydrazones 1 with CH2¼CHCH2Br (2)a)
Entry
R
Product
Time [min]
Yield [%]b)
Ref.
a
b
c
d
e
f
g
h
i
j
k
l
m
n
Ph
4-FꢀC6H4
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
40
40
35
42
45
40
50
45
35
40
45
50
35
40
89
88
84
91
87
85
93
87
89
91
86
93
85
90
[3b,c]
4-ClꢀC6H4
4-BrꢀC6H4
4-MeOꢀC6H4
4-iPrꢀC6H4
3,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2
3-NO2ꢀC6H4
4-CNꢀC6H4
furan-2-yl
[3h,i]
[3i]
[3h,f]
[3d]
[3a]
[3c,f]
[3g]
[3h,i]
[3b,d]
thiophen-2-yl
iPr
Me(CH2)4
a) Reaction conditions: N-benzoylhydrazone 1 (1 mmol), allyl bromide (2; 2.2 mmol), Zn (5 mmol),
THF (3 ml), and aq. NH4Cl soln. (3 ml); reaction at 08. b) Yield of pure isolated compound after column
chromatography.
within 35 – 50 min, and the allylated products 3 were formed in excellent yields (85 –
94%; Table).
For the hydrazone preparation, aromatic, heteroaromatic, and aliphatic aldehydes
were used. The aromatic aldehydes contained both electron-donating and electron-
withdrawing groups. Earlier in some syntheses of 3, the N-benzoylhydrazones derived
from aromatic aldehydes containg an electron-donating group were the only ones used
[3e][3h]. Longer reaction times and unsatisfactory yields are also the drawbacks
associated with various previous methods. For example, the N-benzoylhydrazone 1k
derived from furan-2-carboxaldehyde afforded the allylated product 3k with our
method in 45 min with a yield of 86% (Table, Entry k), while an earlier method [3c]
using allyltributylstannane and SnCl4 required more than 20 h to furnish the same
product 3k from 1k with a yield of 56%. Another drawback of the previous methods
was the utilization of costly reagents and catalysts such as Sc(OTf)3 [3a], while our
method requires the highly available and less costly metal Zn and an aqueous NH4Cl
solution. Organic reactions in aqueous media have been highly encouraged in recent
years due to eco-economic benefits. In our method, an aqueous medium was
successfully utilized for the preparation of N-(but-3-en-1-yl)hydrazide derivatives.
1
The structures of the products were established from their spectral (IR, H- and
13C-NMR, and MS) and anal. data.
Conclusion. – We developed an efficient, cost-effective, and high-yielding method
for the allylation of N-benzoylhydrazones. The mild reaction conditions, rapid
conversions, simple experimental procedure, and the aqueous reaction medium are
the notable advantages of the method.

Helvetica Chimica Acta – Vol. 94 (2011)
1479
The authors thank the Council of Scientific and Industrial Research (CSIR), New Delhi, for financial
assistance.
Experimental Part
Reaction of N-Benzoylhydrazones with Allyl Bromide: General Procedure. To a soln. of an N-
benzoylhydrazone 1 (1 mmol, 266 mg) in THF (3 ml), activated Zn powder (5 mmol, 327 mg) and
CH2¼CHCH2Br (2; 2.2 mmol, 0.2 ml) were added at 08, and the mixture was stirred for 2 – 5 min. Then,
sat. NH4Cl soln. (3 ml) was added dropwise at 08, and the soln. was stirred for 20 – 30 min at r.t. The
mixture was extracted with AcOEt (2 ꢁ 10 ml), the org. layer dried (anh. Na2SO4) and concentrated, and
the residue subjected to column chromatography (SiO2, hexane/AcOEt): pure allylated product 3.
N’-[1-(4-Fluorophenyl)but-3-en-1-yl]benzohydrazide (3b): IR: 3306, 1638, 1517, 1465, 1217.
1H-NMR: 7.81 (br. s, 1 H); 7.60 (d, J ¼ 8.0, 2 H); 7.49 – 7.25 (m, 6 H); 7.04 – 6.92 (m, 2 H); 5.73 (m,
1 H); 5.18 – 5.02 (m, 2 H); 4.11 (t, J ¼ 7.0, 1 H); 2.31 – 2.34 (m, 2 H). 13C-NMR: 167.1; 162.2 (d, J ¼ 280);
137.2; 132.8; 131.7; 129.2; 128.5; 127.0; 118.1; 115.1 (d, J ¼ 10.0); 63.0; 40.2. ESI-MS: 285 ([M þ H]þ).
Anal. calc. for C17H17FN2O: C 71.38, H 5.99, N 9.86; found: C 71.41, H 6.03, N 9.91.
N’-[1-(4-Isopropylphenyl)but-3-en-1-yl]benzohydrazide (3f): IR: 3285, 1641, 1517, 1461, 1308.
1H-NMR: 7.77 (br. s, 1 H); 7.61 (d, J ¼ 8.0, 2 H); 7.51 – 7.24 (m, 6 H); 7.19 (d, J ¼ 8.0, 2 H); 5.82 (m, 1 H);
5.23 – 5.08 (m, 2 H); 4.12 (t, J ¼ 7.0, 1 H); 2.90 (m, 1 H); 2.56 – 2.43 (m, 2 H); 1.22 (d, J ¼ 7.0, 6 H).
13C-NMR: 167.1; 148.2; 139.0; 134.9; 132.0; 128.8; 128.0; 127.1; 127.0; 117.9; 63.3; 40.1; 33.8; 23.7. ESI-MS:
309 ([M þ H]þ). Anal. calc. for C20H24FN2O: C 77.92, H 7.79, N 9.09; found: C 72.96, H 7.82, N 9.12.
N’-[1-(3,4,5-Trimethoxyphenyl)but-3-en-1-yl]benzohydrazide (3h): IR: 3292, 1641, 1591, 1505, 145.
1H-NMR: 7.71 – 7.59 (m, 3 H); 7.49 – 7.31 (m, 4 H); 6.59 (s, 2 H); 5.81 (m, 1 H); 5.26 – 5.09 (m, 2 H); 4.02
(t, J ¼ 7.0, 1 H); 3.80 (s, 9 H); 2.48 – 2.40 (m, 2 H). 13C-NMR: 168.1; 152.9; 137.0; 135.2; 134.0; 131.8;
130.2; 128.7; 127.2; 117.9; 105.0; 64.9; 60.5; 55.8; 38.9. ESI-MS: 357 ([M þ H]þ). Anal. calc. for
C17H17N3O3: C 67.42, H 6.74, N 7.87; found: C 67.47, H 6.79, N 7.81.
N’-[1-(3-Nitrophenyl)but-3-en-1-yl]benzohydrazide (3i): IR: 3295, 1644, 1607, 1527, 1458. 1H-NMR:
7.72 – 7.60 (m, 3 H); 7.58 – 7.35 (m, 4 H); 7.18 (t, J ¼ 7.0, 1 H); 6.79 – 6.54 (m, 3 H), 5.92 (m, 1 H); 5.21 –
5.10 (m, 2 H); 4.08 (t, J ¼ 7.0, 1 H); 2.52 – 2.47 (m, 2 H). 13C-NMR: 167.3; 148.2; 135.5; 135.0; 132.2; 129.7;
129.0; 127.3; 118.2; 117.1; 116.8; 112.1; 112.0; 64.1; 40.5. ESI-MS: 312 ([M þ H]þ). Anal. calc. for
C17H17N3O3: C 65.60, H 5.47, N 13.51; found: C 65.64, H 5.50, N 13.55.
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Received January 7, 2011