Solvent-free addition reaction of allylzinc bromide and aldimines

Article abstract of DOI:10.1080/00397911.2011.565141

(Chemical Equation Presented) Barbier-type allylation of aldimines with allylzinc bromide took place rapidly under solvent-free conditions. The procedure is environmentally benign and operationally simple, has good regioselectivity, and gives good to exce

Full text of DOI:10.1080/00397911.2011.565141

Synthetic Communications1, 42: 2689–2693, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.565141
SOLVENT-FREE ADDITION REACTION OF ALLYLZINC
BROMIDE AND ALDIMINES
Yumei Zhang, Minghu Han, and Tingli Yan
School of Chemical and Biological Engineering, Lanzhou Jiaotong
University, Lanzhou, China
GRAPHICAL ABSTRACT
Abstract Barbier-type allylation of aldimines with allylzinc bromide took place rapidly
under solvent-free conditions. The procedure is environmentally benign and operationally
simple, has good regioselectivity, and gives good to excellent yields.
Keywords Addition reaction; aldimines; allylzinc bromide; homoallylic secondary
amines; solvent-free
INTRODUCTION
Allylation of imines is an important procedure to produce homoallylic amines,
which are fundamental building blocks in many biologically active compounds.[1–4]
Imines have several inherent characteristics, which include their sensitivity to water,
their relatively low electrophilicity, and their tendency to deprotonate when they are
derived from enolizable carbonyl compounds.[2,5] Therefore, traditional procedures
for synthesis of homoallylic amines involve the exclusion of air and moisture and
the use of dry solvent tetrahydrofuran (THF) or CH3CN, alternative media such
as polyethylene glycol (PEG) or poly(propylene) glycol (PPG), and highly reactive
organometallic reagents.[6–9] However, some of the methods employed earlier are
associated with certain drawbacks such as long reaction times, unsatisfactory yields,
and requirement for a catalyst or a nitrogen atmosphere.
Organozinc reagents have more potential application in organic synthesis
because of their tolerance of a wide range of functionalities. However, their appli-
cations were limited for a long time because of their moderate reactivity. The
poor reactivity of zinc organometallic reagents can be increased by adding a
Received November 22, 2010.
Address correspondence to Yumei Zhang, School of chemical and Biological Engineering, Lanzhou
Jiaotong University, 88 West Anning Road, Lanzhou 730070, China. E-mail: zhangym71@163.com
2689

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Y. ZHANG, M. HAN, AND T. YAN
Scheme 1. The solvent-free addition reaction of allylzinc bromide and aldimines.
transition-metal catalyst such as Cu, Pd, Ni, Co, and Mn.[11–12] In our previous arti-
cle, we found that the reactivity of organozinc could be enhanced dramatically in the
absence of solvent (THF). We reported the solvent-free addition reaction of allylzinc
bromide and carbonyl compounds.[13]
In this article, we report the reactions of allylzinc bromide and aldimines to
give homoallylic secondary amines under solvent-free conditions. At first, allylzinc
bromide was prepared in solvent (THF), then THF was evaporated, and at last allyl-
zinc bromide was reacted with aldimines to give homoallylic secondary amines under
solvent-free conditions. We found that the reactivity of organozinc could be
enhanced dramatically by evaporating THF. Allylzinc bromide can react with differ-
ent kinds of aldimines to give homoallylic secondary amines in a very short time
(5 min) in the absence of solvent. The reaction of organozinc reagents always
requires transition-metal catalyst, N2 atmosphere, anhydrous solvent, and low tem-
perature. However, the reaction of allylzinc bromide and aldimines proceeds well in
normal atmosphere at room temperature following our route. The yields are good,
and the reaction time is very short. The result is shown in Scheme 1 and Table 1.
Imines containing both electron-donating and electron-withdrawing groups in
the aromatic rings were found undergo the conversion smoothly. The corresponding
homoallylic secondary amines were obtained in yields ranging from 82% to 95% for
imines derived from aromatic, -CH3, Cl, F, Br substituted aromatic, and heteroaro-
matic aldehydes. The a,b-unsaturated (3j) and the –OH substituted imines (3e, 3f,
and 3 g) proceeded only with 1,2-additions, and the yields were good.
Table 1. Synthesis of homoallylic secondary amines under solvent-free conditions
No.
R
R1
Yield (%)
Time (min)
3a
3b
3c
3d
3e
3f
C6H5
C6H5
4-FC6H4
4-ClC6H4
C6H5
C6H5
91
86
95
85
82
87
85
5
5
5
5
5
5
5
4-BrC6H4
2-OHC6H4
2-OHC6H4
2-OHC6H4
C6H5
C6H5
4-CH3C6H4
2-CH3C6H4
3g
3h
4-CH3C6H4
86
2
3i
3j
4-ClC6H4
C6H5
95
90
2
5
=
Ph-CH CH

ALLYLZINC BROMIDE AND ALDIMINES
2691
Using the reaction of N-benzylidenebenzenamine with allylzinc bromide as an
example, we investigated the effect of solvent (THF) on the reaction. We found that
removal of THF plays a major role in the reaction. We initially studied the reaction
in the presence of THF and found the reactants did not react with each other at all,
even after a long reaction time(8 h). The reactivity of organozinc could be enhanced
dramatically in the absence of solvent. Allylzinc bromide can react with N-
benzylidenebenzenamine in 5 min without any catalysts under solventless condition,
and the yield was good (86%). The reason[14] is probably that the greater concentration
of reactants in the absence of solvent leads to more favorable kinetics than in solution.
EXPERIMENTAL
Infrared (IR) spectra were measured using an Alpha Centauri Fourier trans-
1
form (FT)–IR spectrophotometer. H NMR spectra (400 MHz) were recorded in
CDCl3 using a Bruker AC-E 400-MHz spectrometer. Mass spectra were performed
on QP-1000A. High-resolution mass spectrometry (HRMS) was performed on an
Apex II FT-ICR. Gas chromatography–mass spectrometry (GC-MS) was measured
by electron impact (EI) ionization at 70 eV. Purification of products was performed
via flash chromatography with 200- to 400-mesh silica gel [petroleum ether (bp 60–
90 ꢀC)–ethyl acetate, 20:1]. The chemicals were obtained from commercial sources.
Preparation of the Imines
The imines were prepared by mixing various aldehyde with aniline in the pres-
ence of a catalytic amount of toluene-4-sulfonic acid at room tempreture.[15] The fur-
furaldehyde imines (3 h and 3i) were produced by grinding together furfuraldehyde
with aniline in a mortor in an icebath.
Preparation of Homoallylic Amine
Allylzinc bromide was prepared in an N2 atomosphere using the Knochels
procedure,[12] which has been slightly modified. In a flame-dried, round-bottom flask
fitted with a magnetic bar and dropping funnel, zinc powder (0.39 g, 6 mmol) was
placed and the flask was flashed with dry nitrogen. Zinc powder was heated to
60–70 ꢀC. 1,2-Dibromoethane (0.1 ml, 1.2 mmol) and THF (1 ml) were dropped,
and the temperature was kept for 10 min and then cooled to room temperature.
Trimethyl-chlorosilane (0.1 ml, 0.8 mmol) and THF (0.5 ml) were added. The mix-
ture was stirred at room temperature for 15 min. After this step, allyl bromide
(0.5 g, 5 mmol) in 3 ml THF was added dropwise over 30 min and then stirred for
2 min. Solvent THF was evaporated from the solution of allylzinc bromide in a
rotory evaporator, and aldimine (4 mmol) was added immediately. The resulting
mixture was stirred for 5 min at room temperature. After the reaction was com-
pleted, saturated aqueous ammonium chloride was poured into the mixture and stir-
red for 5 min. Ethyl ether was added to the reaction mixture, and the organic layer
was separated. The organic extracts were dried over anhydrous MgSO4. The residue
was purified by flash chromatography on silica gel to obtain pure product. All the
1
isolated products were characterized by IR, H NMR, 13C NMR, MS, and HRMS.

2692
Y. ZHANG, M. HAN, AND T. YAN
The spectral data for compounds 3a,[16] 3b,[17] 3c,[18] 3d,[18] 3e,[19] 3i,[20] and 3j[17] are
consistent with those reported in the literature. The physical and spectra data for
compounds 3f, 3g, and 3h are as follows.
2-(1-(p-Toluidino)but-3-enyl)phenol (3f)
Oil, IR (cmꢁ1): 3385, 1610, 1563, 1237. 1H NMR: d 9.89 (br s, 2H, OH þ NH),
7.24–6.65 (m, 8H, Ar), 5.87–5.77 (m, 1H, H3), 5.29–5.24 (m, 2H, H4), 4.26 (t, 1H, H1,
J ¼ 6.8 Hz), 2.64 (t, 2H, H2, J ¼ 7.6 Hz), 2.21 (s, 3H, CH3). 13C NMR: d 156.7, 144.1,
134.3 130.8, 129.7, 128.5, 127.7, 126.1, 119.9, 119.6, 117.1, 116.9, 60.4, 41.4, 20.5.
EI-MS m=z (%): 254 (0.41) [Mþ þ 1], 253 (1.41) [Mþ], 212 (100.00), 91 (33.48), 77
(21.78). HRMS calcd for C17H19NO [M þ H]þ: 254.1539; found: 254.1535.
2-(1-(o-Toluidino)but-3-enyl)phenol (3g)
1
Oil, IR (cmꢁ1): 3343, 1610, 1562, 1439, 1274. H NMR: d 9.53 (br s, 2H,
OH þNH), 7.23–6.67 (m, 8H, Ar), 5.91–5.80 (m, 1H, H3), 5.34–5.26 (m, 2H, H4),
4.33 (q, 1H, H1, J ¼ 4.8 Hz), 2.76–2.66 (m, 2H, H2), 2.21 (s, 3H, CH3). 13C NMR:
d 156.5, 144.5, 134.7, 130.2, 128.4, 127.7, 127.1, 126.2, 125.0, 120.7, 120.0, 119.8,
117.1, 114.4, 59.5, 41.6, 17.5. EI-MS m=z (%): 253 (1.63) [Mþ], 212 (100.00), 77
(56.72). HRMS calcd. for C17H19NO [M þ H]þ: 254.1539; found: 254.1543.
N-(1-(Furan-2-yl)but-3-enyl)-4-methylbenzenamine (3h)
1
Oil, IR (cmꢁ1): 3418, 1603, 1505, 1315. H NMR: d 7.36–6.38 (m, 7H, Ar),
5.80–5.71 (m, 1H, H3), 5.19–5.10 (m, 2H, H4), 4.34 (q, 1H, H1, J ¼ 5.2 Hz), 4.04
(br s, 1H, NH), 2.62–2.43 (m, 2H, H2), 2.16 (s, 3H, CH3). 13C NMR: d 145.0,
143.7, 134.7, 129.5, 128.5, 126.8, 126.5, 126.3, 118.1, 113.6, 57.4, 43.2, 20.3. EI-MS
m=z (%): 227 (1.73) [Mþ], 186 (100.00), 77 (37.65), 41 (39.90). HRMS calcd. for
C15H17NO [M þ H]þ: 228.1383; found: 228.1380.
ACKNOWLEDGMENT
This work was supported by the Qing Lan Talent Engineering Funds of
Lanzhou Jiaotong University.
REFERENCES
1. Enders, R. D.; Reinhold, U. Tetrahedron: Asymmetry 1997, 8, 1895.
2. Bloch, R. Chem. Rev. 1998, 98, 1407.
3. Kouznetsov, V.; Urbina, J.; Palms, A.; Lopez, S.; Devia, C.; Bnriz, R.; Zacchino, S.
Molecules 2000, 5, 428.
4. Urbina, J. M.; Cortes, J. C. G.; Palms, A.; Lopez, S. N.; Zacchino, S. A.; Bnriz, R. D.;
Ribas, J. C. Bioorg. Med. Chem. 2000, 8, 691.
5. Johannsen, M.; Jørgensen, K. A. Chem. Rev. 1998, 98, 1689.
6. Einhorn, C., Luche, J. L. J. Organomet. Chem. 1987, 322, 177.
7. Andrews, P. C.; Peatt, A. C.; Raston, C. L. Green Chem. 2004, 6, 119.

ALLYLZINC BROMIDE AND ALDIMINES
2693
8. Wang, D. K.; Dai, L. X.; Hou, X. L.; Zhang, Y. Tetrahedron Lett. 1996, 37, 4187.
9. Fan, R. H.; Pu, D. M.; Qin, L. H.; Wen, F. Q. J. Org. Chem. 2007, 72, 3149.
10. Knochel, P.; Perea, J. J. A.; Jones, P. Tetrahedron 1998, 54, 8275.
11. Men, X.; Wang, K.; Wang, J.-X.; Shi, X. Chin. J. Org. Chem. 2004, 24, 825.
12. Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem. 1988, 53, 2390.
13. Zhang, Y.; Jia, X.; Wang, J.-X. Eur. J. Org. Chem. 2009, 2983.
14. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
15. Andrews, P. C.; Peatt, A. C.; Raston, C. L. Tetrahedron Lett. 2004, 45, 243.
16. Das, B.; Ravikanth, B.; Thirupathi, P.; Rao, B. V. Tetrahedron Lett. 2006, 47, 5041.
17. Yadav, J. S.; Ather, H.; Rao, P. P.; Rao, R. S.; Nagaiah, K.; Prasad, A. R. Catal.
Commun. 2006, 7, 797.
18. Yin, Y.; Zhao, G.; Li, G. Tetrahedron. 2005, 61, 12042.
19. Xie, Z.; Li, G.; Zhao, G.; Wang, J. Chin. J. Chem. 2009, 27, 925.
20. Kouznetsov, V. V.; Vargas, L. Y.; Gupta, M. P.; Freile, M.; Enriz, R. D.; Zacchino, S. A.
Bioorg. Med. Chem., 2008, 16, 794.

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