Alkynylation of benzotriazole with silylethynyliodonium triflates. Regioselective synthesis of 2-ethynyl-2H-benzotriazole derivatives

Article abstract of DOI:10.1021/jo2015467

Phenyl(trimethylsilylethynyl)iodonium and tert-butyldimethylsily- lethynyl(phenyl)iodonium triflates were applied to alkynylation of benzotriazole. Treatment of the silylethynyliodonium triflates with the potassium salt of benzo-triazole ion in ^t

Full text of DOI:10.1021/jo2015467

NOTE
pubs.acs.org/joc
Alkynylation of Benzotriazole with Silylethynyliodonium Triflates.
Regioselective Synthesis of 2-Ethynyl-2H-benzotriazole Derivatives
Tsugio Kitamura,* Mohammad Hasan Morshed, Satoru Tsukada, Yuki Miyazaki, Naomi Iguchi, and
Daisuke Inoue
Department of Chemistry and Applied Chemistry, Graduate School of Science and Engineering, Saga University, Honjo-machi,
Saga 840-8502, Japan
S Supporting Information
b
ABSTRACT: Phenyl(trimethylsilylethynyl)iodonium and tert-butyldimethylsily-
lethynyl(phenyl)iodonium triflates were applied to alkynylation of benzotriazole.
Treatment of the silylethynyliodonium triflates with the potassium salt of benzo-
triazole ion in tBuOH and CH2Cl2 gave 2-(trimethylsilylethynyl)-2H-1,2,3-benzo-
triazole and 2-(tert-butyldimethylsilylethynyl)-2H-1,2,3-benzotriazole in 74% and
76% yields, respectively. The regioisomers, 1-silylethynyl-1H-1,2,3-benzotriazole derivatives, were minor. In both cases of the silyl-
substitued ethynyliodonium salts, novel regioselective alkynylation of benzotriazole at the 2 position was observed.
enzotriazoles belong to one of the important compounds in
nitrogen-containing heterocycles, and they have been widely
as stable compounds and have been applied to UV absorbents.2
To the best of our knowledge, there are no reports on direct and
regioselective functionalization of benzotriazole at the 2 position.
In this paper, we want to report this novel N-2 alkynylation of
benzotriazole as a new method for synthesis of 2-alkynyl-2H-
1,2,3-benzotriazoles.
B
used for organic synthesis as a synthetic auxiliary.1 In addition,
benzotriazoles are useful for functional materials,2 pharmaceu-
ticals, and agricultural chemicals.3 The parent 1,2,3-benzotriazole
exists predominantly as the 1H isomer over the 2H isomer
because of its stability.4 Therefore, most benzotriazoles studied
so far include 1H-1,2,3-benzotriazole derivatives.
First, silylethynyliodonium salts, phenyl(trimethylsilylethynyl)-
iodonium triflate (1a) and tert-butyldimethylsilylethynyl(phenyl)-
iodonium triflate (1b), were synthesized by the reactions of the
corresponding 1,2-bis(silyl)acetylenes with PhI(OAc)2/TfOH
in CH2Cl2, according a literature procedure.10 The outline of
synthesis and reaction of silylethynyliodonium triflates 1 is
shown in Scheme 2. Then, when silylethynyliodonium triflate
1a was treated with potassium salt of benzotriazole ion in
tBuOH and CH2Cl2 at room temperature for 12 h, 2-(trimethyl-
silylethynyl)-2H-1,2,3-benzotriazole (2a) was obtained in 74%
yield. The regioisomer, 1-(trimethylsilylethynyl)-1H-1,2,3-tria-
zole (3a), was obtained in 17% yield. The regioisomers 2a and 3a
were easily distinguishable from 1H and 13C NMR (see Support-
On the other hand, N-ethynyl compounds, as represented by
ynamines, are synthetically valuable, and their significance has
been raised by Katritzky and co-workers.5 Since alkynyliodonium
salts undergo a successive Michael addition/rearrangement reaction
generating alkyne derivatives,6 they can serve as an alkynylation
reagent. Previously, we have found that 1-arylethynyl-1H-1,2,3-
benzotriazoles are obtained selectively by the reaction of
arylethynyl(phenyl)iodonium tosylates using benzotriazole ion
as a nucleophile.7 Although this reaction provides a direct method
introducing an alkynyl group into the 1 position of benzotria-
zoles, there is the serious restriction that this can apply only to
arylethynyl derivatives. Aliphatic alkynyliodinium salts did not
afford the corresponding 1-alkynyl-1H-1,2,3-benzotriazoles.7b
This result suggests that the substituent on the ethynyl group
is required to have a high migratory aptitude. To explore the
scope of this alkynylation reaction, thus we examined phenyl-
(trimethylsilylethynyl)iodonium triflate (1a) as an alkynylating
agent.8
Benzotriazole anion formed by removal of a proton from 1H-
1,2,3-benzotriazole has two resonance forms, as shown in Scheme 1.
Functionalization at the N-1 position gives 1H-benzotriazole
derivatives, whereas functionalization at the N-2 position leads to
the formation of 2H-benzotriazole derivatives.9 In the reaction of
arylethynyliodonium salts, 1-arylethynyl-1H-benzotriazoles were
obtained exclusively.7 Unexpectedly, the reaction of trimethylsi-
lylethynyliodonium triflate 1a gave 2-trimethylsilylethynyl-2H-
benzotriazole as a major product. Although 2H-1,2,3-benzotria-
zole is a minor tautomer, 2-aryl-2H-1,2,3-benzotriazoles are known
1
ing Information). In the H NMR of 2a, two sets of aromatic
protons appeared symmetrically, but the 1H NMR of 3a showed
three sets of aromatic protons. In the 13C NMR, 2a gave only 3
peaks of aromatic carbons, whereas 3a showed the presence of
6 peaks. The reaction of more bulky tert-butyldimethylsilyl-
ethynyliodonium triflate 1b gave 2-(tert-butyldimethylsilyl-
ethynyl)-2H-1,2,3-benzotriazole (2b) and 1-(tert-butyldimethyl-
silylethynyl)-1H-1,2,3-benzotriazole (3b) in 76% and 8% yields,
respectively. In both cases, the reaction of silyl-substitued
ethynyliodonium salts gave 2-ethynyl-substituted benzotriazole
derivatives selectively.
To understand the effect of the silyl group, we studied ethyny-
laton of benzotriazole ion with parent ethynyl(phenyl)iodonium
triflate (1c). Ethynyliodonium triflate 1c was prepared according
Received: July 26, 2011
Published: August 20, 2011
r
2011 American Chemical Society
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Scheme 1. Ambident Character of Benzotriazole Anion for
Functionalization
Scheme 4. Desilylation of 2a
Scheme 5. Possible Mechanism
Scheme 2. Synthesis and Reaction of Silylethynyliodonium
Triflates 1
Scheme 6. Proposal for Preference of N2 Attack
reaction of alkynyliodonium salts with nucleophiles has been
investigated so far,6 the same mechanism is considered to operate
in this reaction. A possible mechanism is illustrated in Scheme 5.
In this way, it is considered that benzotriazole ion attacks on the
β carbon of the alkynyl group to generate an alkenylideneiodo-
nium ylide intermediate, where elimination of phenyliodonio
group occurs to give an alkenylidencarbene. Finally, the alkyny-
lidenecarbene undergoes rearrangement to form an alkynylben-
zotriazole. In the formation of alkynylbenzotriazoles, it is con-
sidered that the migration of silyl groups and a hydrogen atom
takes place rather than a benzotriazolyl group because of their
higher migratory aptitude. In the previous reaction of alkyl-
substituted ethynyliodonium salts,7b rearranged products, i.e.,
alkynylbenzotriazoles, were not obtained at all. This indicates
that the benzotriazolyl group has low migratory ability. However,
the nucleophilic addition of benzotriazole ion gives 1-alkynyl-
and 2-alkynylbenzotriazoles because benzotriazole ion is an
ambident anion. Although a high regioselectivity of 2-alkynyla-
tion by the silyl group is not clear in the present study, it may be
attributable to a bulkiness of the silyl group. The nucleophilic
addition by the N1 atom of the benzotriazole ion may cause a
steric hindrance higher than that by the N2 atom, as shown in
Scheme 6.
Scheme 3. Reaction of Ethynyl(phenyl)iodonium Triflate 1c
to Ochiai’s procedure.11 Treatment of ethynyliodonium triflate 1c
with potassium salt of benzotriazole ion under the same condi-
tions above afforded 2-ethynyl-2H-1,2,3-benzotrizaole (2c) and
1-ethynyl-1H-1,2,3-benzotriazole (3c) in 20% and 52% yields,
respectively (Scheme 3). Although 1-ethynylbenzotriazole 3c gen-
erates predominately, this result suggests that there is no selectivity
because of its almost statistical ratio. It is thought that the high
regioselectivity at the 2 position of benzotriazole ion is attributable
to the effect by a silyl group.
In addition, 2-ethynylbenzotriazole 2c could be obtained from
2-trimethylsilylbenzotriazole 2a. Treatment of 2a with NaOH in
THF/MeOH efficiently afforded 2c in 84% yield (Scheme 4).
Although 2c was unstable under ambient conditions, it was
reasonably characterized by 1H and 13C NMR.
In summary, we have demonstrated that silylethynyliodonium
triflates undergo regioselective alkynylation at the 2 position
of benzotriazole to give 2-silylethynyl-2H-1,2,3-benzotriazoles as
a major product. Desilylation of 2-(trimethylsilylethynyl)ben-
zotriazole 2a generates a parent 2-ethynylbenzotrizole 2c in a
high yield.
The effect of the silyl group on the preferential formation of
2-alkynylation of benzotriazole is not clear. However, since the
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’ EXPERIMENTAL SECTION
67.5À69 °C. 1H NMR (300 MHz, CDCl3) δ 0.29 (s, SiMe2, 6H), 1.06
(s, Me, 9H), 7.43À7.47 (m, ArH, 2H), 7.82À7.85 (m, ArH, 2H); 13C
NMR (75 MHz, CDCl3) δ À5.0, 16.7, 26.0, 76.0, 93.3, 118.1, 128.7,
144.5. HRMS (EI) calcd for C14H19N3Si 257.1348, found 257.1346.
1-(tert-Butyldimethylsilylethynyl)-1H-1,2,3-benzotriazole
(3b). The product was obtained in 8% yield as light yellow crystals, mp
48À49 °C. 1H NMR (300 MHz, CDCl3) δ 0.29 (s, SiMe2, 6H), 1.06 (s,
Me, 9H), 7.43À7.49 (m, ArH, 1H), 7.63À7.65 (m, ArH, 2H), 8.11 (d,
J = 8.1 Hz, ArH, 1H); 13C NMR (75 MHz, CDCl3) δ À4.7, 16.6, 26.1,
82.2, 88.0, 110.1, 120.5, 125.3, 129.4, 134.3, 143.7. HRMS (EI) calcd for
C14H19N3Si 257.1348, found 257.1351.
General. All solvents and starting materials were used as received
without further purification. Melting points were measured with a micro
melting apparatus and are uncorrected. Column chromatographic
separations were carried out using silica gel as the stationary phase.
Precoated plates (silica gel 60 F254) were used for TLC examination. 1,2-
Bis(tert-butyldimethylsilyl)acetylene12 and phenyl(trimethylsilylethynyl)-
iodonium triflate (1a)10 were prepared according to the literature.
Synthesis of tert-Butyldimethylsilylethynyl(phenyl)iodo-
nium Triflate (1b). Trifluoromethanesulfonic acid (1.59 mL, 18 mmol)
was added dropwise to a solution of (diacetoxy)iodobenzene (3.22 g,
10 mmol) in CH2Cl2 (40 mL) at 0 °C. After 30 min of stirring, bis(tert-
butyldimethylsilyl)acetylene (2.55 g, 10 mmol) was added, and the
mixture was stirred at room temperature for 2 h. After evaporation of the
solvent, the residue was washed by decantation with hexane and then
dissolved in CH2Cl2. The solution of CH2Cl2 was washed with water
and dried over anhydrous Na2SO4. Evaporation of CH2Cl2 gave 3.15 g
(64%) of 1b as colorless crystals, mp 131À132.5 °C (hexane/CH2Cl2).
1H NMR (300 MHz, CDCl3) δ 0.17 (s, Me, 6H), 0.91 (s, Me, 9H), 7.52
(t, J = 7.5 Hz, ArH, 2H), 7.65 (t, J = 7.5 Hz, ArH, 1H), 8.07 (d, J = 7.5 Hz,
ArH, 1H); 13C NMR (75 MHz, CDCl3) δ À5.3, 16.7, 25.7, 44.2, 77.2,
117.0, 132.3, 132.5, 133.9. Anal. Calcd for C15H20F3IO3SSi: C, 36.59; H,
4.09. Found: C, 36.32; H, 4.02.
2-Ethynyl-2H-1,2,3-benzotriazole (2c). The product was ob-
1
tained in 20% yield as colorless crystals, mp 63À63.5 °C. H NMR
(300 MHz, CDCl3) δ 3.48 (s, tCH, 1H), 7.42À7.48 (m, ArH, 2H),
7.81À7.87 (m, ArH, 2H); 13C NMR (75 MHz, CDCl3) δ 61.8, 74.6,
118.2, 128.9, 144.6. HRMS (EI) calcd for C8H5N3 143.0483, found
143.0481.
1-Ethynyl-1H-1,2,3-benzotriazole (3c)14. The product was
obtained in 52% yield as colorless crystals, mp 81À81.6 °C. 1H NMR
(300 MHz, CDCl3) δ 3.87 (s, tCH, 1H), 7.45À7.50 (m, ArH, 1H),
7.61À7.70 (m, ArH, 2H), 8.12 (d, J = 8.4 Hz, ArH, 1H); 13C NMR
(75 MHz, CDCl3) δ 68.5, 69.5, 109.9, 120.6, 125.4, 129.6, 134.3, 143.7.
Preparation of 2-Ethynyl-2H-1,2,3-benzotriazole (2c) by
Desilylation of 2a. To a solution of 2a (0.108 g, 0.5 mmol) in THF
(1 mL) and MeOH (1 mL) was added 1 M NaOH solution (1 mol/L,
0.5 mL) dropwise, and the mixture was stirred for 5 min. The product
was extracted with CH2Cl2 and separated by column chromatography
on silica gel. Elution with CH2Cl2/hexane gave 2c as colorless crystals in
84% yield.
Synthesis of Ethynyl(phenyl)iodonium Triflate (1c)13. A
solution of trimethylsilylethynyliodonium triflate 1a (0.9006 g, 2 mmol)
in CH2Cl2 (4 mL) was prepared in a Teflon tube. Aqueous HF (56%,
0.14 mL) was added, and the mixture was stirred at room temperature
for 2 h. To the reaction mixture was added anhydrous Na2SO4, and the
mixture was filtrated. Concentration of the solution gave 0.578 g (76%)
1
of 1c as colorless crystals, mp 111.5À113 °C (hexane/CH2Cl2). H
’ ASSOCIATED CONTENT
NMR (300 MHz, CDCl3) δ 3.24 (s, tCH, 1H), 7.53À7.58 (m, ArH,
2H), 7.67À7.72 (m, ArH, 1H), 8.08À8.11 (m, ArH, 2H); 13C NMR
(75 MHz, CD3CN) δ 29.7, 97.9, 117.4, 121.3, 133.2, 133.8, 136.0.
Reaction of Silylethynyliodonium Triflates 1a and 1b with
Benzotriazole Ion. To a solution of tBuOK (0.168 g, 1.5 mmol) in
tBuOH (10 mL) was added dropwise a solution of benzotriazole (0.179 g,
1.5 mmol) in CH2Cl2 (10 mL). The mixture was stirred at room
temperature for 1 h and diluted with CH2Cl2 (10 mL). The solution of
the potassium salt of the benzotriazole ion thus prepared was added
dropwise to a solution of silylethynyliodonium triflate 1 (1.0 mmol) in
CH2Cl2 (10 mL), and the mixture was stirred at room temperature for
12 h. The reaction mixture was poured into water, and the product was
extracted with CH2Cl2. The CH2Cl2 extract was washed with water and
brine and dried over anhydrous Na2SO4. After evaporation of the
solvent, the product was separated by column chromatography with
hexane/CH2Cl2 as eluent. The product was further purified by recrys-
tallization from CH2Cl2/hexane.
Supporting Information. 1H and 13C NMR spectra of
S
b
alkynylbenzotriazoles 2aÀ2c and 3aÀ3c. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: kitamura@cc.saga-u.ac.jp.
’ REFERENCES
(1) For reviews:(a) Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko,
O. V. Chem. Rev. 1998, 98, 409–548. (b) Katritzky, A. R.; Manju, K.;
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2-Trimethylsilylethynyl-2H-1,2,3-benzotriazole (2a). The
product was obtained in 74% yield as colorless crystals, mp 76.5À
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1
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SiMe3, 9H), 7.42À7.47 (m, ArH, 2H), 7.80À7.86 (m, ArH, 2H); 13
C
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NMR(75 MHz, acetone-d6) δ À0.6, 77.2, 93.7, 118.7, 129.8, 145.2. Anal.
Calcd for C11H13N3Si: C, 61.36; H, 6.09; N, 19.51. Found: C, 61.50; H,
6.12; N, 19.35.
1-Trimethylsilylethynyl-1H-1,2,3-benzotriazole (3a). The
product was obtained in 17% yield as brown oil. 1H NMR (300 MHz,
CDCl3) δ 0.26 (s, SiMe3, 9H), 7.32À7.37 (m, ArH, 1H), 7.49À7.62 (m,
ArH, 2H), 7.99 (d, J = 8.4 Hz, ArH, 1H); 13C NMR (75 MHz, CDCl3)
δ À0.3, 83.7, 87.4, 110.1, 120.4, 125.2, 129.3, 134.1, 143.6. Anal. Calcd
for C11H13N3Si: C, 61.36; H, 6.09; N, 19.51. Found: C, 61.63; H, 6.00;
N, 19.51.
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2-(tert-Butyldimethylsilylethynyl)-2H-1,2,3-benzotriazole
(2b). The product was obtained in 76% yield as colorless crystals, mp
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