Construction of 3-aryl-1,2,4-benzotriazines via unprecedented rearrangement of bis(benzotriazol-1-yl)methylarenes

Article abstract of DOI:10.1016/j.tetlet.2010.10.093

3-Aryl-1,2,4-benzotriazines were formed unexpectedly by the treatment of 1,l-bis(benzotriazol-1-yl)methylarenes with allylsamarium bromide. A radical pathway was proposed involving steps, such as fragmentation, ring-opening, and cyclization.

Full text of DOI:10.1016/j.tetlet.2010.10.093

Tetrahedron Letters 51 (2010) 6763–6766
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Construction of 3-aryl-1,2,4-benzotriazines via unprecedented
rearrangement of bis(benzotriazol-1-yl)methylarenes
Zhiyun Zhong a,b, Ran Hong b, Xiaoxia Wang a,
⇑
a Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, Zhejiang 321004, PR China
b CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, CAS, 345 Fenglin Lu, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
3-Aryl-1,2,4-benzotriazines were formed unexpectedly by the treatment of 1,l-bis(benzotriazol-1-yl)
methylarenes with allylsamarium bromide. A radical pathway was proposed involving steps, such as
fragmentation, ring-opening, and cyclization.
Received 19 July 2010
Revised 15 October 2010
Accepted 18 October 2010
Available online 26 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Bifunctional derivatives bearing two leaving groups on one car-
bon, such as L–CH–L0 (L and L0 are leaving groups), constitute a
class of useful substrates for the installation of multi-functional-
ities through proper transformations.1 Cleavage of the bond of C–
L or C–L0 and deprotonation depend on the leaving ability of L
rangement of 1 was observed. Herein, we wish to report our preli-
minary results.
Bis(benzotriazolyl)arylmethanes 1 were previously synthesized
from substituted benzaldehydes,10a
a,a
-dichlorotoluenes,6 or
benzaldehyde dimethylacetal.10b However, only limited examples
were disclosed. A referential preparation of alkylidenebisamides,
which contained an N–CH–N building block, was conducted by
the condensation of aldehydes with amides.11 It is apparent that
the condensation of 1 equiv of aldehyde with 2 equiv of benzotria-
zole may provide a direct method for the synthesis of the desired
bis(benzotriazolyl) methylarenes (Scheme 2).
and L0 groups and the acidity of the
a-H under specific conditions.
For example, the cleavage of the C–halogen bond occurred prefer-
entially over the C–H bond when (benzotriazol-1-yl)-1-chloroalk-
anes were treated with phenol in the presence of sodium
hydroxide.2 Deprotonation proceeded to give carbanions when
(benzotriazol-1-yl)-1-ethoxylalkanes,3 (benzotriazol-1-yl)methyl
thioether,4a and (benzotriazol-1-yl)-1-carbazolylalkanes4b were
treated with butyllithium. With the following addition of appropri-
ate electrophiles (e.g., alkyl halides, aldehydes, ketones, and imi-
nes), a variety of ketone derivatives can be synthesized.
To our delight, with PTSA as a catalyst, the reaction of benzotri-
azole with aromatic aldehyde in refluxing toluene proceeded
smoothly to generate bis(benzotriazolyl) methylarenes 1 and 2 in
moderate to good combined yields. In all the cases, two isomers,
As a good leaving group and activating moiety, benzotriazolyl
(Bt) plays an important role in the preparation of a variety of com-
pounds.5 The gem-Bt compounds (Bt–CH–Bt) already showed
interesting applications in organic synthesis. For example, bis(ben-
zotrizaol-1-yl)methylarenes could form carbanions at 0 °C with the
treatment of LDA6 or potassium tert-butoxide.7 Reactions of the
carbanions with alkyl, benzyl, or allyl halides gave the correspond-
ing alkylated products in good yields, while reactions with acid ha-
lides and cyclohexenone led to the masked 1,2- and 1,4-diketones.7
In continuation of our research on the application of benzotria-
zole in organic synthesis, we attempt to synthesize homoallylic
benzotriazoles. In our previous study, allylsamarium bromide
was found to smoothly substitute one of the acyloxy group in
1,10-diacetates to afford homoallylic esters.8 We envisioned that
allylsamarium reagent would undergo a Barbier-type reaction with
bis(benzotriazol-1-yl)methylarenes 1 to form homoallylic amine
derivatives (Scheme 1).9 Interestingly, an unprecedented rear-
namely, 1,l-bis(benzotriazol-1-yl)methylarenes 1 and 1-(ben-
zotriazol-1-yl)-l-(benzotriazol-2-yl)methylarenes 2 (Table 1) were
obtained.12 The 1,l-adduct 1 was isolated as the major product.
Aromatic aldehydes with an electron-withdrawing group were
found to afford slightly better yields of 1 than those bearing an
electron-donating group.
When bis(benzotriazolyl)methyl arenes 1a was subjected to the
freshly prepared allylsamarium bromide in THF, the characteristic
violet color of allylsamarium bromide faded gradually and disap-
peared within 1 h. After completion of the reaction, no consider-
able amount of substitution product was isolated. To our
surprise, 3-phenyl-1,2,4-benzotriazine 3a was isolated instead
along with a debenzotriazolyl compound 4a (Scheme 3).
N
N
N
SmBr
N
N
N
N
N
N
H
H
Ar
Ar
1
⇑
Corresponding author. Tel.: +86 579 82283702; fax: +86 579 82282595.
E-mail address: wangxiaoxia@zjnu.cn (X. Wang).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.093

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Z. Zhong et al. / Tetrahedron Letters 51 (2010) 6763–6766
3-Aryl-1,2,4-benzotriazines 3 have been prepared by the oxida-
rearranged to 3-phenyl- and 3-p-tolyl-1,2,4-benzotriazines,
respectively, by opening the benzotriazole ring.14a The formation
of 3a and 4a (the structures were ascertained by NMR and by com-
parison with literature data) under the mild conditions from read-
ily available materials intrigued us to develop an alternative useful
method for the synthesis of 3-aryl-1,2,4-benzotriazines.
tion of N-phenylsulfonyl-N00-arylbenzamidrazones with mer-
cury(II) oxide through a diazonium intermediate.13 It was also
reported that, when treated by 3 equiv of n-butyllithium in the
presence of TMEDA, two specific
a-(benzotriazol-1-yl)hydrazones
Thus, a variety of bis(benzotriazol-1-yl)methylarenes were sub-
sequently investigated under the same reaction conditions.15 As
dictated in Table 2, the reaction has general applicability and deliv-
ers moderate to good yields of product 3. The electron-donating or
withdrawing group on the aryl did not have a distinct influence on
the yield of the 3-aryl-1,2,4-benzotriazines (Table 2, entries 1–10).
It remains unclear why 1d afforded 3d in a relatively lower yields.
It should also be mentioned that 1i failed to produce the desired
product 3i and only 4i was isolated in 68% yield under the opti-
mized conditions.
Ar
N
N
N
N
N
N
O
1
N
TsOH H2O
toluene
N
+
H
2
N
Ar
N
H
N
N
N
N
N
Ar
The formation of 3 obviously resulted from a rearrangement of
1 through a ring-opening of benzotriazole. The benzotriazole ring
usually is stable to acids and bases, oxidation and reduction, and
heat. Nevertheless, opening of the benzotriazole ring in certain
benzotriazole derivatives has been observed. Photolysis- and pyro-
lysis-induced ring opening of benzotriazole were usually accompa-
nied by the extrusion of N2.16a Grignard reagent induced specific
benzotriazoles to undergo the ring-opening via the nucleophilic at-
tack.16b,c Base-catalyzed or amine-promoted ring-opening of ben-
zotriazoles with electron-withdrawing substituents were also
reported.16d–f We previously reported a reductive ring-opening of
N-acylbenzotriazoles, where a cascade of ring-opening and ring-
closure resulted in 1-acylamidobenzimidazoles.16g Since the ring-
opening of gem-Bt compounds was previously unknown, several
conditions were examined to get insights into the reaction
mechanism.
2
Scheme 2.
Table 1
Synthesis of bis(benzotriazolyl)arylmethanes from the condensation of aromatic
aldehydes and benzotriazole
Entry Ar
Products Mp (lit. °C)
Yieldsa
(%)
143–145 (lit.10a 144–
1a
2a
46
16
146)
1
134–135 (lit.10a 134–
135)
180–182 (lit.10a 183–
1b
2b
40
13
Me
185)
2
122–124 (lit.10a 123–
In the presence of a base, such as n-butyllithium and potassium
tert-butoxide, the ring-opening reaction of bis(benzotriazol-1-
yl)methylarenes 1a did not take place. When allylmagnesium bro-
mide was used as an alternative reagent of allylsamarium bromide,
the ring-opening reaction failed to occur either. These results
apparently did not support a carbanion intermediate.
125)
1c
2c
158–160
106–108
29
8
3
4
5
6
MeO
Cl
1d
2d
120–121
104–105
57
19
1e
2e
138–140
128–129
55
19
In light of the good reducing ability of divalent samarium re-
agent, such as SmI2, a probable single electron transfer (SET) mech-
anism is proposed as shown in Scheme 4. First, allylsamarium
bromide reacts with one of the benzotriazoles of 1a through a frag-
mentation process to form a benzyl radical A along with a benzot-
rizolyl Sm(III) complex. The radical species A may abstract a
hydrogen atom from the solvent to form benzyl benzotriazoles
4a as a by-product. And meanwhile, it may induce a ring-opening
of triazole to form intermediate B, which subsequently reassem-
bles to form a new ring system like 3-phenyl-1,2,4-benzotriazine
radical (C). After expelling the hydrogen, benzotriazines 3a was
generated. On the other hand, the Sm(III) complex can be
quenched by the solvent to give benzotriazole. The formation of
benzotriazole was closely related to the amount of 3a and 4a
(determined by the crude 1H NMR analysis of the reaction mix-
ture), which indicates the intermediate A was indeed a precursor
to 3a and 4a as shown in the proposed mechanism. To further ver-
ify this free radical process, bis(benzotriazol-1-yl)arylmethane 1a
Br
1f
2f
117–119
102–103
59
19
F
1g
2g
161–163
118–120
41
13
7
8
H3C
1h
2h
145–147
107–109
44
16
H3CO
1i
2i
129–131
113–114
50
18
9
Cl
1j
2j
125–127
116–117
49
10
10
Br
a
The reaction time was 36 h; Isolated yields based on aldehydes.
N
N
N
N
SmBr
THF
N
N
N
N
+
Ar
N
N
C
Ar
N
N
H
Ar
3
4
1
Scheme 3.

Z. Zhong et al. / Tetrahedron Letters 51 (2010) 6763–6766
6765
Table 2
Formation of 3-aryl-1,2,4-benzotriazines via ring-scissions of 1,l-bis(benzotriazol-1-yl)methylarenes
Entry
1
Ar
Products
Mp (lit. °C)
Yieldsa (%)
3a
4a
123–124 (lit.13 124–126)
114–115 (lit.14b 114–115)
40
49
1a
3b
4b
116–118 (lit.13 119–120)
104–106 (lit.14b 108–109)
43
45
Me
MeO
Cl
2
3
4
5
6
1b
1c
3c
4c
140–142 (lit.13 143–144)
—
65
Traceb
3d
4d
148–150 (lit.13 150–152)
92–94 (lit.14c 101–102)
29
60
1d
1e
3e
4e
134–136
56
39
120–122 (lit.14d 118–119)
Br
3f
4f
144–146
44
45
71–72 (lit.14d 68–69)
F
1f
3g
4g
105–106
51
42
116–117 (lit.14d 116–117)
7
8
H3C
1g
3h
4h
102–103
55
37
51–52 (lit.14e 54–55)
H3CO
1h
3i
4i
—
Traceb
68
57–58 (lit.14b
)
9
Cl
1i
3j
4j
164–166
—
54
Traceb
10
Br
1j
a
The reaction time was 1 h; isolated yields based on 1,l-bis(benzotriazol-1-yl)methylarenes.
Detected by GC–MS.
b
N
N
N
N
N
N
N
N
BrSm
N
N
N
N
N
Sm
Br
N
N
H
A
Br
Sm
N
N
1a
N
N
N
hydrogen
N
benzotriazole
abstraction
H
hydrogen
Bt
abstraction
N
4a
N
N
N
N
H
H
N
N
N
N
N
N
A
N
N
fragmentation
N
H
N
H
B
C
3a
Scheme 4.
was treated with SmI2, a typical SET reagent. It was gratifying to
find that both 3a and 4a were obtained at room temperature over
8 h in comparable isolated yields (3a, 52%; 4a, 19%).
In conclusion, an improved preparation of bis(benzotriazol-1-
yl)metylarenes has been developed by the direct condensation
of benzotriazole with arylaldehydes. In addition, allylsamarium
bromide was found to be a single-electron transfer agent for
the first time, which induced an unprecedented and novel radical
rearrangement of the bis(benzotriazol-1-yl)metylarenes to give
benzotriazines in moderate to good yields. The alternative ap-
proach to the synthesis of 3-aryl-1,2,4-benzotriazines was thus
established.

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Z. Zhong et al. / Tetrahedron Letters 51 (2010) 6763–6766
10. (a) Katritzky, A. R.; Kuzmierkiewicz, W.; Rachwal, B.; Rachwal, S.; Thomson, J. J.
Acknowledgments
Chem. Soc., Perkin Trans. 1 1987, 811; (b) Ballesteros, P.; Elguero, J.; Claramunt,
R. M. Tetrahedron 1985, 41, 5955.
We are grateful to the National Natural Science Foundation of
China (No. 20802070) (to X.X.W.) and SRF for ROCS, SEM (to
R.H.) for financial support. We also thank Professor Gangguo Zhu
for helpful discussions.
11. Noyes, W. A.; Forman, D. B. J. Am. Chem. Soc. 1933, 55, 3493.
12. General procedure: To
a solution of aromatic aldehyde (10 mmol) and
benzotriazole (20 mmol) in toluene (50 mL) was added PTSA (20 mol %). The
mixture was then refluxed for 36 h (monitored by TLC). The resulting brown
reaction mixture was cooled to room temperature and extracted with ethyl
acetate (3 ꢀ 20 mL). The combined extracts were washed successively with
saturated sodium bicarbonate and brine, dried over anhydrous sodium sulfate,
and concentrated under reduced pressure. The residue was subjected to
purification on silica gel chromatography (PE:EA = 4:1) to give 1,l-
bis(benzotriazol-yl)alkanes (1a–j) and 1-(benzotriazol-1-yl)-l-(benzotriazol-
2-yl)methylarenes (2a–j).
Supplementary data
Supplementary data (the spectral data of compounds 1–4, and
the 1H NMR, 13C NMR spectra of compounds 1–3 can be found in
the online version) associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.093.
13. Suketake, I.; Yumo, T.; Akikazu, K. Bull. Chem. Soc. Jpn 1982, 55, 859.
14. (a) Katritzky, A. R.; Wang, J.; Karodia, N.; Li, J. Q. Synth. Commun. 1997, 27,
3963; (b) Katritzky, A. R.; Gordeev, M. F.; Greenhill, J. V.; Steel, P. J. J. Chem. Soc.,
Perkin Trans. 1 1992, 1111; (c) Katritzky, A. R.; Toader, D.; Xie, L. J. Org. Chem.
1996, 61, 7571–7577; (d) Kang, Y. H.; Kim, K. J. Heterocycl. Chem. 1997, 34,
1741; (e) Katritzky, A. R.; Zhang, G. F.; Xie, L. H. J. Org. Chem. 1997, 62, 721.
15. Procedure for the rearrangement of 1a: To a two-necked flask, samarium (0.33 g,
2.2 mmol) and allyl bromide (0.30 g, 2.5 mmol) in THF (20 mL) were added at
room temperature under nitrogen. When the color of the mixture turned
purple, stirring was continued for an additional 1 h until the samarium powder
disappeared. 1,l-Bis(benzotriazol-yl)alkanes 1a (1.0 mmol) were added to the
solution, and the resulting mixture was stirred at room temperature for 1 h. A
saturated solution of sodium potassium tartrate (5 mL) was added to quench
the reaction and the corresponding mixture was extracted with ethyl acetate
(3 ꢀ 10 mL). The combined organic layers were washed with brine (2 ꢀ 10 mL)
and dried over anhydrous MgSO4. The solvent was removed by evaporation
under reduced pressure. The crude product was purified by column
chromatography on silica gel (PE:EA = 6:1) to afford 3-aryl-1,2,4-
benzotriazines 3a (82.8 mg, 40% yield) as yellow solid and benzyl
benzotriazoles 4a (102.4 mg, 49% yield) as light brown solid.
References and notes
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