The barbier reaction of 1-chloromethylbenzo-triazole with imines and successive elimination

Article abstract of DOI:10.1081/SCC-120002403

Under the mediation of samarium diiodide, 1-chloromethyl-benzotriazole 1 can undergo Barbier reaction smoothly with imines 2 to produce 1-(β-aminoethyl)benzotriazole 3. Successive elimination of 3 gives imines 7 increased one carbon. The possible mechanis

Full text of DOI:10.1081/SCC-120002403

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THE BARBIER REACTION OF 1-CHLOROMETHYLBENZO-
TRIAZOLE WITH IMINES AND SUCCESSIVE ELIMINATION
Zhizhen Huang a , Hongwei Jin a & Dehui Duan a
a Department of Chemistry , Zhejiang University at Xixi Campus , Hangzhou, 310028, P.
R. China
Published online: 16 Aug 2006.
To cite this article: Zhizhen Huang , Hongwei Jin & Dehui Duan (2002) THE BARBIER REACTION OF 1-
CHLOROMETHYLBENZO- TRIAZOLE WITH IMINES AND SUCCESSIVE ELIMINATION, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 32:4, 565-570, DOI: 10.1081/SCC-120002403
To link to this article: http://dx.doi.org/10.1081/SCC-120002403
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SYNTHETIC COMMUNICATIONS, 32(4), 565–570 (2002)
THE BARBIER REACTION
OF 1-CHLOROMETHYLBENZO-
TRIAZOLE WITH IMINES AND
SUCCESSIVE ELIMINATION
Zhizhen Huang,* Hongwei Jin, and Dehui Duan
Department of Chemistry, Zhejiang University at
Xixi Campus, Hangzhou 310028, P. R. China
ABSTRACT
Under the mediation of samarium diiodide, 1-chloromethyl-
benzotriazole 1 can undergo Barbier reaction smoothly
with imines 2 to produce 1-(b-aminoethyl)benzotriazole 3.
Successive elimination of 3 gives imines 7 increased one
carbon. The possible mechanism is proposed as well.
It is well known that benzotriazole is an important and versatile
auxiliary group in organic synthesis.1 Among numerous benzotriazole com-
pounds, 1-chloromethyl benzotriazole is one of the most basic benzotriazole
derivatives, from which a large amount of benzotriazole compounds can be
prepared. In general, imines are not so easily to undergo nucleophilic addi-
tion with organometallic reagents, which result in some side reactions, such
as coupling reaction, enolization or reduction.2,3
*Corresponding author.
565
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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HUANG, JIN, AND DUAN
In the course of studies on the application of benzotriazole compounds
in organic synthesis, we found that, under the mediation of samarium diio-
dide, 1-chloromethylbenzotriazole can react with aldehydes and ketones to
produce 1-(b-hydroxylalkyl)benzotriazoles.4 Here we wish to report the
SmI2-Barbier reaction of 1-chloromethylbenzotriazole 1 with imine 2 as a
new electrophile.
Under the action of samarium diiodide, 1-chloromethylbenzotriazole 1
can be converted to the precursor of benzotriazolylmethyl anion, which then
undergoes nucleophilic addition with imines (see Scheme 1). Experimental
Scheme 1.
results showed that, in the solution of samarium diiodide in THF, 1-chlor-
omethylbenzotriazole 1 can react with imines 2 rapidly at r.t., giving
1-(b-aminoalkyl)benzotriazoles 3 in the yields of 61–80% (see Table 1).
No coupling product of imine 2 was observed. The reaction condition is
milder than that in previous synthesis from (1-chloromethyl)benzotriazole 1,
which needs strong base (LDA) and low temperature (ꢀ78ꢁC).5
Table 1. The SmI2-Barbier Reaction of 1-Chloromethylbenzotriazole 1 with Imines 2
Products
Ar
Ar0
M.P. (ꢁC)
Isolated Yield (%)
3a
3b
3c
3d
3e
Ph
Ph
Ph
129–131
112–113
119–121
118–120
104–104
80
60
61
71
65
p-CH3C6H4
m-BrC6H4
Ph
Ph
p-CH3C6H4
p-ClC6H4
p-CH3C6H4
Cl
3f
p-CH3C6H4
134–136
78–80
60
80
Cl
3g
p-CH3OC6H4
Ph

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1-CHLOROMETHYLBENZOTRIAZOLE
567
Successive elimination of 1-(b-aminoethyl)benzotriazoles 3 with
t-BuOK in DMF gives imines 7, which increase one carbon in comparison
with the original imines 2. Although the base and solvent used in the elim-
ination reaction (1) is the same as that in the reaction (2)5, the eliminating
product is the imine 7 rather than alkyne 5, which is interesting in mechan-
ism. From the result it can be inferred that, in the reaction (2), t-BuOK
abstracts a-H in 1-(b-aminoethyl)benzotriazole 3 to eliminate BtH at first,
then abstracts b-H to eliminate ArNH2 further because aryl group can be
functioned as an electron withdrawing group to increase the acidity of b-H,
whereas the elimination reaction (2) stopped at the product of enamine 6
because the acidity of b-H in 6 is weaker than that in 4 (see Scheme 2).
Scheme 2.
In conclusion, 1-chloromethylbenzotriazole 1 can undergo Barbier
reaction very smoothly with imines 2 to give 1-(b-aminoethyl)benzotriazole
3 in the presence of samarium diiodide. This method has the advantages of
mild reaction condition, readily available starting material, simple manip-
ulation and good yield. The successive elimination of 1-(b-aminoethyl)ben-
zotriazoles 3 affords a new method for the synthesis of imines 7 and its result
gives the mechanism of the elimination of 3.
EXPERIMENTAL
1H NMR spectra were determined in CDCl3 on a Brucker AM300
(300 MHz) or JEOL PMX60SI (60 MHz) with TMS as internal standard.

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HUANG, JIN, AND DUAN
IR spectra were recorded on a PE683 spectrometer and mass spectra were
obtained on a HP5989 mass spectrometer. Elemental analyses were per-
formed at Carlo-Erba 1106 instrument. Melting points were uncorrected.
(1-Chloromethyl)-benzotriazole was prepared according to the literature
method.6
General Procedure for the Synthesis of
1-(b-Aminoethyl)benzotriazoles 3a–g
To the solution of samarium diiodide (0.81 g, 2.0 mmol) in THF
(20 ml), was added the mixed solution of imine (1.0 mmol) and (1-chloro-
methyl)-benzotriazole (0.17 g, 1.0 mmol) in THF (5 ml) under nitrogen. The
reaction mixture was stirred at room temperature for 5 min. Then aqueous
solution of hydrochloric acid (0.1 M, 2 ml) was added and the mixture was
extracted with ethyl acetate (20 ml  2). The organic layer was washed with
saturated solution of sodium thiosulfate and sodium chloride and dried over
magnesium sulfate. After concentration under reduced pressure, the residue
was subjected to preparative TLC (Petroleum ether : Ethyl acetate ¼ 4 : 1 as
eluent) to yield 3a–g.
1
Compound 3a. H NMR d (ppm): 8.03 (d, 1H, J ¼ 8.0 Hz), 7.38–7.16
(m, 6H), 7.07–7.04 (m, 2H), 6.82–6.79 (m, 2H), 6.65 (t, 1H, J ¼ 7.3 Hz),
6.53–6.50 (t, 2H, J ¼ 7.7 Hz), 4.94–4.86 (m, 3H), 4.78 (s, 1H). IR n
(cmꢀ1): 3440, 3080, 3050, 2900, 1650, 1620, 1610, 1550, 1465, 1440, 1365,
1325, 1245, 1185, 962, 750, 700. MS m/e (relative intensity): 315 (Mþ þ 1, 8),
196 (5), 182 (100), 104 (30), 77 (45). Anal. Calc. for C20H18N4: C, 76.4; H,
5.7; N, 17.8; Found: C, 76.1; H, 5.5; N, 17.9.
1
Compound 3b. H NMR d (ppm): 8.03 (d, 1H, J ¼ 8.1 Hz), 7.35–7.25
(m, 7H), 7.12 (d, 1H, J ¼ 8.1 Hz), 6.86 (d, 2H, J ¼ 8.4 Hz), 6.43 (d, 2H,
J ¼ 8.4 Hz), 4.87–4.95 (m, 4H), 2.15 (s, 3H). IR n (cmꢀ1): 3395, 3030,
2950, 1630, 1530, 1468, 1300, 1230, 810, 745, 705. MS m/e (relative inten-
sity): 328(M þ, 8), 210 (4), 196 (100), 118 (15), 104 (5), 91 (20), 77 (18). Anal.
Calc. for C21H20N4: C, 76.8; H, 6.1; N, 17.1; Found: C, 76.6; H, 6.2; N, 17.4.
1
Compound 3c. H NMR d (ppm): 8.03 (d, 1H, J ¼ 7.9 Hz), 7.36–7.25
(m, 7H), 7.09 (d, 1H, J ¼ 8.0 Hz), 6.89 (t, 1H, J ¼ 8.1 Hz), 6.76–6.67 (m, 1H),
6.65–6.64 (m, 1H), 6.40 (m, 1H), 5.00–4.89 (m, 4H). IR n (cmꢀ1): 3395, 3030,
2940, 2870, 1620, 1520, 1510, 1260, 1200, 1040, 830, 745, 690. MS m/e
(relative intensity): 393 (Mþ, 25), 275 (5), 260 (100), 222 (3), 182 (18), 156
(15), 133 (8), 104 (10), 77 (30). Anal. Calc. for C20H17N4: C, 61.1; H, 4.3, N,
14.2; Found: C, 61.4; H, 4.4; N, 14.4.
1
Compound 3d. H NMR d (ppm): 7.97 (d, 1H, J ¼ 8.3 Hz), 7.30–6.96
(m, 9H), 6.57 (d, 1H, J ¼ 7.3 Hz), 6.43 (d, 2H, J ¼ 8.4 Hz), 4.87–4.80 (m, 3H),

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1-CHLOROMETHYLBENZOTRIAZOLE
569
4.67 (s, 1H) 2.23 (s, 3H). IR n (cmꢀ1): 3395, 3030, 2940, 1648, 1620,
1525, 1510, 1260, 1235, 820, 780, 750, 690. MS m/e (relative intensity):
329 (Mþ þ 1, 15), 210 (10), 196 (100), 118 (5), 104 (20), 91 (18), 77 (28).
Anal. Calc. for C21H20N4: C, 76.8; H, 6.1; N, 17.1; Found: C, 76.5; H, 6.0;
N, 17.4.
1
Compound 3e. H NMR d (ppm): 7.97 (d, 1H, J ¼ 8.3 Hz), 7.35–7.13
(m, 6H), 7.07 (d, 1H, J ¼ 7.9 Hz), 6.80 (d, 2H, J ¼ 8.2 Hz), 6.33 (d, 2H,
J ¼ 8.4 Hz), 4.86–4.79 (m, 3H), 4.64 (s, 1H), 2.08 (s, 3H). IR n (cmꢀ1):
3400, 3340, 3040, 2950, 1630, 1530, 1500, 1280, 1090, 1020, 810, 740. MS
m/e (relative intensity): 363 (Mþ, 10), 246 (5), 230 (100), 194 (5), 118(15),
104 (4), 91 (12), 77 (8). Anal. Calc. for C20H18N4: C, 69.7; H, 5.0; N, 9.8;
Found: C, 69.2; H, 4.7; N, 9.2.
1
Compound 3f. H NMR d (ppm): 8.03 (d, 1H, J ¼ 8.6 Hz), 7.48–7.32
(m, 4H), 7.18(d, 1H, J ¼ 8.4 Hz), 7.04–7.01 (m, 1H), 6.86 (d, 2H,
J ¼ 8.2 Hz), 6.31 (d, 2H, J ¼ 8.3 Hz), 5.22–4.89 (m, 4H), 2.14 (s, 3H). IR
n (cmꢀ1): 3395, 3040, 2940, 1650, 1625, 1600, 1530, 1520, 1480, 1290,
1240, 1170, 1050, 810, 795, 745. MS m/e (relative intensity): 397 (Mþ, 15),
228(8), 118(10), 91 (20), 77 (15). Anal. Calc. for C 21H17N4Cl: C, 63.6, H,
4.3; N, 14.1; Found: C, 63.3; H, 4.1; N, 14.3.
1
Compound 3g. H NMR d (ppm): 7.96 (d, 1H, J ¼ 8.3 Hz), 7.31–6.97
(m, 7H), 6.74 (d, 2H, J ¼ 8.6 Hz), 6.67–6.63 (t, 1H, J ¼ 7.3 Hz), 6.45 (d, 2H,
J ¼ 7.8 Hz), 4.87–4.85 (m, 4H), 3.68 (s, 3H). IR n (cmꢀ1): 3400, 3040, 2950,
2870, 1650, 1620, 1520, 1510, 1310, 1250, 1180, 1040, 860, 750, 690. MS m/e
(relative intensity): 344 (Mþ, 2), 212 (100), 180 (3), 119 (3), 104 (25), 91 (5),
77 (25). Anal. Calc. for C20H18N4: C, 73.5; H, 5.8; N, 16.3; Found: C, 73.1;
H, 5.5; N, 16.4.
General Procedure for the Synthesis of Imines 7a–b
Under nitrogen, the solution of 1-(b-aminoethyl)benzotriazoles 3
(1.0 mmol) and t-BuOK (95%, 0.35 g, 3.0 mmol) in dry DMF (10 ml)
was stirred at room temperature for 1 h. To the reaction mixture was
added ice water (15 ml) and then it was extracted with diethyl ether
(20 ml  3). The combined extracts were washed with water (20 ml), dried
over magnesium sulfate and evaporated under reduced pressure. The residue
was subjected to preparative TLC (petroleum ether : ethyl acetate ¼ 5 : 1 as
eluent) to give imine 7a–b.
Compound 7a. Yield: 55%. Mp: 39–41ꢁC; Lit7: 40–41ꢁC. H NMR d
1
(ppm): 7.40–6.81 (m, 10H), 2.16 (s, 3H). IR n (cmꢀ1): 3030, 1650, 1600,
1505, 1350, 1250, 1100, 745, 700.

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HUANG, JIN, AND DUAN
Compound 7b. Yield: 58%. Mp: 90–92ꢁC; Lit7: 94ꢁC. 1H NMR d
(ppm): 7.95 (d, 2H, J ¼ 8Hz), 7.31–6.61 (m, 7H), 3.80 (s, 3H), 2.15 (s, 3H).
IR n (cmꢀ1): 3040, 1640, 1500, 1350, 1265, 1100, 780, 700.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China for the
financial support of the project 29972036.
REFERENCES
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Meltz, C.N. J. Am. Chem. Soc. 1983, 105, 5946. d) Mori, K.;
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Received in the UK November 20, 2000

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