Synthesis of homoallylic amines and acylhydrazides by tin powder-promoted multicomponent one-pot allylation reactions

Article abstract of DOI:10.1002/aoc.3472

An efficient process for the synthesis of homoallylic amines and N′-homoallylic hydrazides is developed from the one-pot reaction of carbonyl compounds, amines or N-acylhydrazines, allyllic bromide and tin powder using water as solvent. N-Acylhydrazines are found to be more reactive than amines in these processes. They can react not only with aldehydes but also with ketones to give the corresponding N′-homoallylic hydrazides. Copyright

Full text of DOI:10.1002/aoc.3472

Full paper
Received: 11 November 2015
Revised: 3 February 2016
Accepted: 9 February 2016
Published online in Wiley Online Library: 6 April 2016
(wileyonlinelibrary.com) DOI 10.1002/aoc.3472
Synthesis of homoallylic amines and
acylhydrazides by tin powder-promoted
multicomponent one-pot allylation reactions
Junyan Ma, Danfeng Huang*, Ke-Hu Wang, Yanli Xu, Siying Chong,
Yingpeng Su, Ying Fu and Yulai Hu*
An efficient process for the synthesis of homoallylic amines and N′-homoallylic hydrazides is developed from the one-pot reaction
of carbonyl compounds, amines or N-acylhydrazines, allyllic bromide and tin powder using water as solvent. N-Acylhydrazines are
found to be more reactive than amines in these processes. They can react not only with aldehydes but also with ketones to give
the corresponding N′-homoallylic hydrazides. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: tin powder; multicomponent reaction; homoallylic amines; homoallylic hydrazides; allylation
pot allylation reactions of aldehydes, amines and allylic bromide
Introduction
in 1,4-dioxane to give homoallylic amines in good yields.[61] In our
Allylation of carbonyl and imino groups is one of the most
convenient and efficient methods for synthesis of homoallylic
compounds,[1–8] which are versatile building blocks in the
preparation of many biologically active molecules and natural
products.[9–21] As reported in the literature, allylic organometallics
such as allylic Mg,[22,23] Zn,[24,25] In,[26–29] Sn,[30–38] Si,[39,40] B[25,41]
and Sm[42,43] have been intensively investigated in allylation reac-
tions. Among these organometallics, allylic stannanes have been
widely used because of their easy availability, air and moisture sta-
bility, tolerance to functional groups and high selectivity.[44–46]
However, most stannanes are toxic.[47,48] Furthermore, only the allyl
group in allylic stannanes is delivered into the product molecules
and the other residues are usually discarded as waste after the reac-
tions. In 1981, Mukaiyama and Harada[49] reported that combina-
tion of tin and allylic bromide or iodide could replace allylic
stannanes in allylation of aldehydes or ketones to give the corre-
sponding allylic alcohols in organic solvents, but the yield was less
than 50%. Subsequently, Nokami and co-workers reported that ad-
dition of water to the reaction system could accelerate the reaction
and increase the product yields up to 75%.[50] This is unique consid-
ering strictly anhydrous operations compared to other traditional
organometallic reagents. Subsequently, allylations mediated by
metallic tin were investigated in the presence of water or just using
water as solvent, but most studies focused on allylation of
aldehydes.[31,51–55] Some other substrates such as nitroalkenes,[11]
enol ethers[56] and aldoximes[57] were also allylated using allylic
bromide and metallic tin in water to give homoallylic alcohols.
In view of various advantages of tin-promoted reactions, we are
interested in developing some new reactions mediated by metallic
tin, especially reactions in water because water is considered to be
the cleanest solvent available to synthetic chemists.[58–60] In our
previous investigation, we found tin powder could promote one-
on-going studies, we found that acylhydrazines could replace
amines in a similar reaction using water as solvent. In particular,
acylhydrazines could react not only with aldehydes but also with
less reactive ketones to afford N′-homoallylic hydrazides, which
are relatively new scaffolds found in a wide variety of biologically
active molecules,[62–64] and also show potential applications in
material science (Scheme 1).[65–69] Herein, we report our results
concerning these one-pot allylation reactions in water.
Results and discussion
Initially, the one-pot allylation reaction of aldehydes and amines
was investigated in water. Thus, aniline (1a; 1 equiv.), benzaldehyde
(2a; 1 equiv.), allylic bromide (3; 1.5 equiv.) and tin (2.5 equiv.) were
mixed in water, and stirred at room temperature for 24 h. After
work-up, the desired product 4a is obtained in 47% yield and by-
product 5a, which is formed from double allylation of aniline, is also
obtained in 20% yield (Table 1, entry 6). In order to increase the
yield of 4a and improve chemoselectivity, the reaction conditions
were examined next. The results are summarized in Table 1. It is
found that the molar ratio of substrates has great influence on
the yield and selectivity. When the ratio of aniline, benzaldehyde
and allylic bromide is fixed at 1/1/1, the yield of 4a increases with
*
Correspondence to: Danfeng Huang or Yulai Hu, College of Chemistry and
Chemical Engineering, Northwest Normal University, Anning East Road 967,
Lanzhou, Gansu 730070, PR China. E-mail: huangdf@nwnu.edu.cn; huyl@nwnu.
edu.cn
College of Chemistry and Chemical Engineering, Northwest Normal University,
Anning East Road 967, Lanzhou, Gansu, 730070, People’s Republic of China
Appl. Organometal. Chem. 2016, 30, 571–576
Copyright © 2016 John Wiley & Sons, Ltd.

J. Ma et al.
Table 2. Reaction of various amines and various aldehydes for the one-
pot synthesis of homoallylic aminesa
Entry
R1
R2
Yield (%)b
Scheme 1. One-pot allylation for the synthesis of homoallylic amines and
hydrazides.
4
5
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4a (83)
4b (54)
4c (65)
4d (70)
4e (45)
4f (74)
4 g (79)
4 h 82)
4i (79)
4j (86)
4 k (78)
4 l (75)
4 m (72)
4n (61)
4o (78)
4p (79)
4q (82)
4r (65)
4 s (87)
4 t (90)
4u (0)c
4v (0)
5a (trace)
5b (16)
increasing amount of metal tin (Table 1, entries 1–5), but stops in-
creasing when the amount of tin is above 2.5 equiv. (Table 1, entries
4 and 5). The amount of allylic bromide also affects the yield of 4a,
which increases with increasing allylic bromide. A reasonable
amount of allylic bromide is found to be 2.0 equiv. (Table 1, entries
6–8). It is worth noticing that 5a is always formed in a yield of
around 20% in every experiment when the ratio of aniline and
benzaldehyde is fixed at 1/1 (Table 1, entries 3–8). Thus, the ratio
of aniline and benzaldehyde was checked again. With the propor-
tion of benzaldehyde increasing, the yield of 4a increases quickly,
and 5a cannot be detected (Table 1, entries 9–11). Finally, the
best molar ratio of 1a/2a/3/Sn was determined to be 1.0/1.5/2.0/
2.5 (Table 1, entry 10).
Under the optimized reaction conditions, we investigated the
generality of the allylation reaction with respect to a range of
amines and aldehydes. The results are collected in Table 2. Firstly,
different amines were reacted with benzaldehyde. It is found
that all the aromatic amines can react with benzaldehyde
smoothly to give the desired products 4 (Table 2, entries 1–7), but
aliphatic amines such as n-BuNH2 and t-BuNH2 cannot produce
products 4 (Table 2, entries 21 and 22). Aromatic amines with
electron-withdrawing groups produce the products in slightly
higher yields than with electron-donating groups. This can be
2
p-MeC6H4
o-MeC6H4
Mes
3
5c (trace)
5d (trace)
5e (18)
4
5
p-MeOC6H4
p-BrC6H4
p-ClC6H4
Ph
6
5f (trace)
5 g (trace)
5a (12)
7
8
p-MeOC6H4
o-ClC6H4
o-FC6H4
2-Thienyl
2-Furyl
9
Ph
5a (trace)
5a (trace)
5a (trace)
5a (trace)
5c (trace)
5b (10)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Ph
Ph
Ph
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
o-FC6H4
o-FC6H4
o-FC6H4
o-FC6H4
Ph
o-MeC6H4
p-MeC6H4
p-ClC6H4
p-BrC6H4
o-MeC6H4
p-MeC6H4
p-ClC6H4
p-BrC6H4
n-Bu
5 g (trace)
5f (trace)
5c (trace)
5b (trace)
5 g (trace)
5f (trace)
5 h (trace)
5i (trace)
5a (68)
Ph
t-Bu
n-Pr
Ph
4w (0)
aReaction conditions: amines (1, 1.0 mmol), aldehydes (2, 1.5 mmol),
allylic bromide (3, 2.0 mmol), tin (2.5 mmol), H2O (4.0 ml).
bIsolated yield.
cHomoallylic alcohol (hept-1-en-4-ol) was obtained in 47% yield.
Table 1. Optimization of reaction conditions for one-pot synthesis of
homoallylic aminesa
explained in terms of the inductive effect. We believe that the reac-
tion starts with the formation of imines, which then react with allylic
tin species formed in situ to give the products. As shown in Fig. 1,
electron-withdrawing groups on aromatic amines can make the in
situ generated imines more electrophilic, and thus accelerate the
reaction to form the products in higher yields. However, when
the inductive effect of the substituents on aromatic amines is
the same, such as electron-donating groups, the amines with
ortho-substituents afford products in slightly higher yield than with
para-substituents (Table 2, entries 2 and 3). This may be due to the
steric hindrance around the amine group. The ortho-substituents of
aromatic amines give more steric hindrance around the amine
group than the para-substituents. This steric hindrance slows down
the direct allylation of amine groups, which leads to the formation
of 5. For instance, 5b is obtained in 16% yield when p-methylaniline
is used (Table 2, entry 2). However, when o-methylaniline or more
hindered mesidine is used, 5c or 5d cannot be obtained (Table 2,
entries 3 and 4).
Entry
Mole ratio of
1a/2a/3/Sn
Time (h)
Yield (%)b
4a
5a
1
1.0/1.0/1.0/1.0
1.0/1.0/1.0/1.5
1.0/1.0/1.0/2.0
1.0/1.0/1.0/2.5
1.0/1.0/1.0/3.0
1.0/1.0/1.5/2.5
1.0/1.0/2.0/2.5
1.0/1.0/2.5/2.5
1.0/1.2/2.0/2.5
1.0/1.5/2.0/2.5
1.0/2.0/2.0/2.5
24
24
24
24
24
24
24
24
12
12
12
0
0
Trace
15
2
Trace
13
3
4
42
12
5
38
17
6
47
20
7
53
18
8
52
21
9
74
Trace
Trace
Trace
10
11
83
79
aReaction conditions: aniline (1a, 1.0 mmol), benzaldehyde (2a, 1.0–
2.0 mmol), allylic bromide (3, 1.0–2.5 mmol), tin (1.0–3.0 mmol), H2O
(4.0 ml).
bIsolated yield.
Next, various aldehydes were reacted with aniline to test the
scope of these substrates (Table 2, entries 8–12). The results show
electron-donating or electron-withdrawing groups on phenyl rings
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Appl. Organometal. Chem. 2016, 30, 571–576

Tin-promoted synthesis of homoallylic amines and acylhydrazides
Table 3. Optimization of reaction conditions for one-pot synthesis of N
′-homoallylic hydrazidesa
Entry Mole ratio Catalyst Amount of
T
Time Yield (%)b
of 2a/9a/3/
catalyst
(mol%)
(°C)
(h)
Figure 1. Effects of substituents of arylamines on electrophilicity of imines
formed in situ.
10a 11
Sn
1
1/1.5/2/2.5
—
—
10
10
10
10
10
10
5
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
45
65
85
56
36
27
32
27
36
36
52
35
27
27
27
27
27
27
27
27
27
27
27
27
0
62
37
24
33
35
20
23
30
24
20
19
25
22
21
17
10
12
13
8
of aromatic aldehydes have little influence on the yields of the
products 4. Investigation of synergistic effects of substituents on
both aromatic amines and aromatic aldehydes reveals that
yields of 4 are higher when the substituents on both amines and
aldehydes are electron-withdrawing groups. In contrast, the
yield is lower when the substituents on both amines and
aldehydes are electron-donating groups (Table 2, entries 13–20).
When an aliphatic aldehyde such as butyraldehyde is used, the
desired product 4w does not form, but 5a is obtained in 68% yield
(Table 2, entry 23).
In order to further investigate the generality of the substrate
scope, aldehydes were replaced by ketones in the reaction. For in-
stance, cyclohexanone (6a) was reacted with aniline, allylic bromide
and tin powder under the reaction conditions mentioned above,
but there is no desired product 7 formed at room temperature after
24 h. After raising the reaction temperature to 60 °C, only allylic al-
cohol 8 is obtained in 63% yield (Scheme 2). The reason is that
the corresponding ketimine cannot be formed during the
reaction because there is no ketimine detected even after aniline
and cyclohexanone were allowed to react under the same reaction
conditions for 12 h.
2
1/1.5/2/2.5 PhCOOH
1/1.5/2/2.5 TsOH
1/1.5/2/2.5 TFA
1/1.5/2/2.5 TfOH
1/1.5/2/2.5 HCl
1/1.5/2/2.5 H2SO4
1/1.5/2/2.5 TfOH
1/1.5/2/2.5 TfOH
1/1.5/2/2.5 TfOH
1/1.5/2/2.5 TfOH
1/1.5/2/2 TfOH
1/1.5/2/3 TfOH
1/1.5/2/3.5 TfOH
1/1.5/3/2.5 TfOH
1/1.5/4/2.5 TfOH
1/1.5/4.5/2.5 TfOH
1/1.5/5/2.5 TfOH
1/1.5/4/2.5 TfOH
1/1.5/4/2.5 TfOH
1/1.5/4/2.5 TfOH
1/1.5/4/2.5 TfOH
12
29
11
33
10
16
26
51
59
58
51
60
58
63
70
68
68
77
3
4
5
6
7
8
9
15
20
25
20
20
20
20
20
20
20
20
20
20
20
10
11
12
13
14
15
16
17
18
19
20
21
22
83 Trace
77 Trace
Reflux 27
35
0
N-Acylhydrazones, which serve as storable and stable imine
equivalents, have attracted increasing attention in organic synthe-
sis in the last decade.[70] Some of their reactions can even proceed
smoothly in water.[71,72] Thus, we aimed to determine if the amines
in the above reaction could be replaced by N-acylhydrazines to af-
ford the corresponding N′-homoallylic hydrazides. The investiga-
tion started by stirring benzaldehyde, benzoylhydrazine (9a),
allylic bromide and tin powder in water at room temperature. After
56 hours, N′-homoallylic hydrazide 10a is not detected and only the
N-acylhydrazone 11 is obtained in 62% yield (Table 3, entry 1). Care-
ful examination shows that addition of 10 mol% of benzoic acid can
catalyze the formation of 10a in 12% yield (Table 3, entry 2). Encour-
aged by this result, other Brønsted acids were tested (Table 3, en-
tries 1–7), and trifluoromethanesulfonic acid (TfOH) is found to be
the best acid. For example, the yield of 10a is improved to 33% with
11 formed in 35% yield at the same time if 10 mol% of TfOH is used
(Table 3, entry 5). The influence of the loading of TfOH was then ex-
amined (Table 3, entries 8–11). It is found that 20 mol% of TfOH
gives the best yield. If the loading of TfOH is above 20 mol%, the
yield does not improve. Also, a study of the mole ratio of substrates
aReaction conditions: benzaldehyde (2a, 1.0 mmol), benzoylhydrazine
(9a, 1.5 mmol), allylic bromide (3, 2.0–5 mmol), tin (2.0–3.5 mmol),
TfOH (5–25 mol%), H2O (4.0 ml).
bIsolated yield.
reveals that the amount of allylic bromide has a great influence on
the product yield. When the ratio of 2a/9a/Sn is fixed at 1/1.5/2.5,
the yield of 10a increases with increasing allylic bromide, but 4
equiv. is a reasonable amount (Table 3, entries 15–18). The reason
for the use of excess allylic bromide is that part of it would be hy-
drolyzed during the reaction. Finally, optimal reaction temperature
was also explored with the results showing that the yield of 10a in-
creases with increasing reaction temperature. The best tempera-
ture is found to be around 65 °C. If the temperature is above
65°C, the yield of 10a decreases; in particular, when the reaction
is performed at reflux, the yield of 10a decreases markedly to
35% (Table 3, entry 22). This might be explained by the acceleration
of hydrolyzation of allylic bromide at high temperature during the
reaction.
Table 4 summarizes the results of expanding the range of various
aldehydes and N-acylhydrazines under the above optimized
reaction conditions. Most of the tested aromatic and aliphatic
aldehydes can react with various N-acylhydrazines in the presence
of allylic bromide and tin to afford the corresponding N′-
homoallylic hydrazides in good yields. As for N-acylhydrazines, all
of the aromatic ones can react smoothly with various aldehydes
Scheme 2. One-pot allylation of cyclohexanone.
Appl. Organometal. Chem. 2016, 30, 571–576
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J. Ma et al.
Table 4. Reaction of various aldehydes and various acylhydrazines for
one-pot synthesis of N′-homoallylic hydrazidesa
Table 5. Reaction of various ketones and aryl acylhydrazines for one-
pot synthesis of N′-homoallylic hydrazidesa
Time (h) Product Yield (%)b
Entry
R1
R4
Time (h) Product Yield (%)b
Entry
R1, R3
R4
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
27
12
13
12
12
12
36
36
12
9
10a
10b
10c
10d
10e
10f
83
82
81
89
79
64
48
0
1
–(CH2)5–
–(CH2)5–
–(CH2)5–
–(CH2)5–
Ph
14
16
13
16
24
24
18
24
24
24
13
18
18
20
36
18
16
36
36
12a
12b
12c
12d
12e
12f
72
68
79
70
54
60
72
53
46
55
75
70
64
43
0
2
p-MeOC6H4
m-MeC6H4
p-MeC6H4
p-FC6H4
p-ClC6H4
2-Furyl
2
p-OMeC6H4
p-ClC6H4
2-Furyl
3
3
4
4
5
5
–CH(CH3)(CH2)4–
p-ClC6H4
6
6
–CH2CH(CH3)(CH2)3– p-ClC6H4
–(CH2)2CH(CH3)(CH2)2– p-ClC6H4
7
10 g
—
7
12 g
12 h
12i
8
Me
8
–(CH2)3–
–(CH2)3–
–(CH2)3–
–(CH2)4–
–(CH2)4–
–(CH2)4–
–(CH2)6–
–(CH2)7–
Me, Me
Ph
9
p-MeOC6H4 Ph
10 h
10i
75
79
85
71
65
60
72
79
83
53
75
65
70
51
78
69
9
p-MeC6H4
p-ClC6H4
p-ClC6H4
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
p-MeC6H4
p-ClC6H4
o-ClC6H4
m-ClC6H4
3-Thienyl
n-Pr
Ph
10
11
12
13
14
15
16
17
18
19
12j
Ph
9
10j
12 k
12 l
12 m
12n
—
Ph
12
17
24
16
11
16
24
18
24
18
24
15
24
10 k
10 l
10 m
10n
10o
10p
10q
10r
Ph
p-MeC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
Ph
Ph
Ph
Bn
Ph
12o
12p
—
62
73
0
Cinnamyl
p-MeC6H4
p-ClC6H4
p-MeC6H4
p-ClC6H4
3-Thienyl
n-Pr
Ph
Me, Et
p-MeC6H4
p-MeC6H4
p-ClC6H4
p-ClC6H4
2-Furyl
p-ClC6H4
p-MeC6H4
Ph, Me
Ph
p-BrC6H4, Me
p-MeC6H4
—
0
10s
10 t
10u
10v
10w
aReaction conditions: ketones (6, 0.5 mmol), acylhydrizines (9,
0.75 mmol), allylic bromide (3, 2.0 mmol), tin (1.25 mmol), H2O (4.0 ml).
bIsolated yield.
Cinnamyl
aReaction conditions: aldehydes (2, 0.5 mmol), acylhydrizines (9,
0.75 mmol), allylic bromide (3, 2.0 mmol), tin (1.25 mmol), H2O
(4.0 ml).
bIsolated yield.
does not give the product at all (Table 5, entry 15). Some ali-
phatic acyclic ketones such as acetone and butanone react to
give products in good yields (Table 5, entries 16 and 17), but
aromatic ketones do not afford the products (Table 5, entries
18 and 19).
Finally, the activities of amines and N-acylhydrazines were in-
vestigated. As shown in Scheme 3, when equal amounts of ani-
line and benzoylhydrazine are reacted with benzaldehyde,
allylic bromide and tin powder in water at room temperature
for 12 h, products 10a from benzoylhydrazine and 5a from dou-
ble allylation of aniline are obtained in 41 and 30% yields, re-
spectively. Product 4a from aniline does not form at all. This
indicates that N-acylhydrazines are more reactive than amines
in the reactions.
to afford the products in good to excellent yields. However, ali-
phatic N-acylhydrazines such as acetohydrazide do not give the
product (Table 4, entry 8).
Although cyclohexanone does not react with aniline in the
presence of allylic bromide and tin in water (Scheme 2), we still
wondered if N-acylhydrazines could replace amines to react with
ketones to produce the corresponding N′-homoallylic hydra-
zides in water. With this idea in mind, cyclohexanone and
benzoylhydrazine were tentatively stirred with allylic bromide
and tin in water at 65 °C for 14 h. To our delight, the desired
product 12a is readily obtained. Afterwards, different kinds of
ketones were reacted with various aromatic N-acylhydrazines
in the presence of allylic bromide and tin in water, and the re-
sults are summarized in Table 5. Cyclohexanone and
cyclopentanone can react with various N-acylhydrazines to give
the products 12 in good yields (Table 5, entries 1–4 and 11–13).
However, when the α-position of cyclohexanone has a substitu-
ent, the yield of the corresponding product is lower (Table 5,
entry 5). Cyclobutanone and cycloheptanone afford products
in lower yields (Table 5, entries 8–10 and 14), but cyclooctanone
Based on the experimental results and the literature,[31,51] a pos-
sible mechanism is tentatively proposed as shown in Scheme 4.
Amines or N-acylhydrazines react with aldehydes or ketones firstly
Scheme 3. Comparison of reactivity of aniline and benzoylhydrazine in
one-pot allylation.
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Tin-promoted synthesis of homoallylic amines and acylhydrazides
4-Methoxy-N′-(1-phenylbut-3-en-1-yl)benzohydrazide (10b). White solid;
0.122g (82%) yield; m.p. 95–96 °C. IR (KBr, νmax, cmÀ1): 3367, 3274,
1
1640, 1482, 1283, 1183, 1023. H NMR (400 MHz, CDCl3, δ, ppm):
7.56–7.54 (m, protons of C13, C17 and NHa, 3H), 7.39–7.24 (m,
5H), 6.84 (d, J = 8.8 Hz, protons of C14 and C16, 2H), 5.88–5.76 (m,
proton of C3, 1H), 5.24 (br, NHb, 1H), 5.18–5.09 (m, protons of C4,
2H), 4.14 (t, J= 8.0Hz, proton of C1, 1H), 3.79 (s, protons of C18,
3H), 2.56–2.42 (m, protons of C2, 2H). 13C NMR (100MHz, CDCl3, δ,
ppm): 166.8 (C11), 162.3 (C15), 141.7 (C5), 134.5 (C3), 128.6, 128.4,
127.7, 127.5, 125.0, 117.8 (C4), 113.7 (C14 and C16), 63.8 (C18),
55.3 (C1), 40.3 (C2). HRMS: calcd for C18H21N2O2 [M + H]+ 297.1598;
found 297.1596. Anal. Calcd for C18H20N2O2 (%): C, 72.95; N, 9.45;
H, 6.80. Found (%): C, 72.87; N, 9.34; H, 6.74. Structure:
Scheme 4. Proposed mechanism for formation of 4, 10 or 12.
to produce intermediate 13. The reaction between allylic bromide
and tin powder affords intermediate 14, which undergoes nucleo-
philic addition reaction to intermediate 13 to give intermediate
16. After hydrolysis of intermediate 16, the products 4, 10 or 12
are produced.
N′-(1-allylcyclohexyl)-4-chlorobenzohydrazide (12c). White solid; 0.115 g
(79%) yield; m.p. 111–112 °C. IR (KBr, νmax, cmÀ1): 3225, 2924,
1624, 1436, 1330, 1086. 1H NMR (400 MHz, CDCl3, δ, ppm):
7.66 (d, J = 8.4 Hz, protons of C3 and C7, 2H), 7.50 (br, NHa,
1H), 7.39 (d, J = 8.4 Hz, protons of C4 and C6, 2H), 6.06–5.93
(m, proton of C10, 1H), 5.24–4.89 (m, NHb and protons of C11,
Conclusions
In summary, an efficient process for the synthesis of homoallylic
amines or N′-homoallylic hydrazides is described. In these
processes, water is used as solvent and a combination of allylic
bromide and tin powder is used to replace toxic allylic stannane
reagents. N-Acylhydrazines are more reactive than amines in these
processes. They can react not only with aldehydes but also with
ketones to give corresponding N′-homoallylic hydrazides. However,
amines do not react with ketones to afford the corresponding prod-
ucts in water.
3H), 2.26 (d, J = 7.2 Hz, protons of C9, 2H), 1.71–1.59 (m, C6H10
,
2H), 1.55–1.36 (m, C6H10, 8H). 13C NMR (100 MHz, CDCl3, δ,
ppm): 165.9 (C1), 137.8 (C5), 134.7 (C10), 131.3 (C2), 128.8 (C3
and C7), 128.2 (C4 and C6), 117.5 (C11), 58.9 (C8), 41.4 (C9),
33.6 (C12 and C16), 25.7 (C13 and C15), 21.9 (C14). HRMS: calcd
for C16H22ClN2O [M + H]+ 293.1415; found 293.1420. Anal. Calcd
for C16H21ClN2O (%): C, 65.63; N, 9.57; H, 7.23. Found (%): C,
65.60; N, 9.35; H, 7.12. Structure:
Experimental
General procedure for synthesis of homoallylic amines and N′-
homoallylic hydrazides
Acknowledgments/Acknowledgements according to UK/US
spelling of paper
Synthesis of compounds 4
We are grateful for financial support from the National Natural
Science Foundation of China (grant nos. 21262031; 21462037);
Key Laboratory Polymer Materials of Gansu Province (Northwest
Normal University); Bioactive Product Engineering Research Center
for Gansu Distinctive Plants; and State Key Laboratory of Applied
Organic Chemistry, Lanzhou University.
Aldehydes 2 (1.5 mmol) and amines 1 (1 mmol) were mixed in water
(4 ml), and then tin powder (2.5 mmol) and allylic bromide 3
(2.0 mmol) were added into the mixture. After being stirred at room
temperature (monitored using TLC), 2 ml of HCl (1 mollÀ1) was
added to quench the reaction. The resulting mixture was extracted
with EtOAc (3 × 10 ml). The combined organic layers were dried over
MgSO4 and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel using petroleum
ether–ethyl acetate (10:1, v/v) as eluent to afford compounds 4.
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