Thermal reaction of 4-(p-aminophenyl)-1-sulfonyl-1,2,3-triazoles furnishing benzoyl cyanides through N-sulfinyl imine intermediates

Article abstract of DOI:10.1246/cl.150320

A thermal reaction of 4-(p-aminophenyl)-1-sulfonyl-1,2,3- triazoles forming benzoyl cyanides is reported. A carbene species thermally generated from the triazole by denitrogenation undergoes intramolecular oxygen migration from sulfur to carbon, giving an N-sulfinyl benzoylimine intermediate. The subsequent Cope-type elimination of the sulfinyl group gives rise to cyano functionality.

Full text of DOI:10.1246/cl.150320

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Thermal Reaction of 4-(p-Aminophenyl)-1-sulfonyl-1,2,3-triazoles Furnishing Benzoyl Cyanides
Through N-Sulfinyl Imine Intermediates
Tomoya Miura,* Qiang Zhao, Yuuta Funakoshi, and Masahiro Murakami*
Advance Publication on the web April 29, 2015 by J-STAGE
doi:10.1246/cl.150320
© 2015 The Chemical Society of Japan
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1
Thermal Reaction of 4-(p-Aminophenyl)-1-sulfonyl-1,2,3-triazoles Furnishing Benzoyl Cyanides
Through N-Sulfinyl Imine Intermediates
Tomoya Miura,* Qiang Zhao, Yuuta Funakoshi, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510
E-mail: tmiura@sbchem.kyoto-u.ac.jp, murakami@sbchem.kyoto-u.ac.jp
2
A thermal reaction of 4-(p-aminophenyl)-1-sulfonyl-
SO2R
N
1
3 N
N
1,2,3-triazoles forming benzoyl cyanides is reported. A
carbene species thermally generated from the triazole by
denitrogenation undergoes intramolecular oxygen migration
from sulfur to carbon, giving an N-sulfinyl benzoylimine
intermediate. The subsequent Cope-type elimination of the
sulfinyl group gives rise to a cyano functionality.
SO2R
N
N
H
SO2R
Ph
(a)
(b)
4
5
(pht)N
(pht)N
H
N(pht)
(ref. 10)
Ph
3
2
1
R
N
SO2R
N SO2R
S
N
N
O
N
O
p-NO2C6H4
NEt2
NEt2
p-NO2C6H4
p-NO2C6H4
NEt2
5
4
Diazo compounds are useful reactive species in organic
synthesis, and are widely utilized as the precursors for the
generation of free carbenes and metal carbene complexes.1
Recently, N-sulfonyl-1,2,3-triazoles possessing aryl and alkyl
groups at the C4-position have received much attention as the
latent precursor of diazo compounds.2 The triazoles are
readily prepared by a copper-catalyzed cycloaddition reaction
of terminal alkynes with sulfonyl azides.3 They are generally
stable compounds to exist in the triazole form, yet generate α-
diazo imines by equilibrium.4 The transient diazo compounds
can be efficiently trapped by transition metal complexes to
furnish the corresponding metal carbene complexes.5 During
the past several years, a number of synthetic transformations
involving those metal carbene complexes have been
developed.6–9 On the other hand, in case N-sulfonyl-1,2,3-
triazoles possess a phthalimido substituent (or a phenoxy
substituent) at the C4-position10 or a diethylamino substituent
at the C5-position,11 they can thermally generate carbene
species without participation of transition metals.12 For
6
(ref. 11)
R
O
O
N
O
N
H
S
SO2R
CN
N
N
(c)
H
N
9
N
8
N
7
(this work)
Figure 1. Transformation of N-sulfonyl-1,2,3-triazoles
possessing amino substituents at various positions.
elimination [Figure 1, (c)].14
Initially,
4-(p-dimethylaminophenyl)-1-mesyl-1,2,3-
triazole (7a) was prepared in 79% yield from (p-
dimethylaminophenyl)acetylene and mesyl azide according to
the literature procedure using a copper catalyst.3d As with the
cases of other 4-aryl-substituted 1-sulfonyl-1,2,3-triazoles, the
equilibrium of ring-chain tautomerization lies far to the
triazole form, and the ring-opened diazo form was not
detected by NMR and IR spectra. The triazole 7a in a solid
state was stable at room temperature for weeks. Nevertheless,
the p-dimethylamino substituent significantly enhanced its
thermal reactivity; 7a in a solution gradually decomposed (t1/2
= ca. 8 h in CDCl3 at room temperature) to form N-sulfinyl
benzoylimine 8a. When 7a in acetonitrile was heated at 80 °C
for 10 min in a sealed microwave vessel under microwave
irradiation (MW), 7a was almost consumed to give a mixture
of 8a (67% NMR yield) and benzoyl cyanide 9a (18% NMR
yield) (Eq 1). Upon heating 7a at the same temperature for a
prolonged time (4 h), 9a was formed in 90% yield as the
example,
4-phthalimido-1-sulfonyl-1,2,3-triazoles
1
[phthalimido = (pht)N-] thermally undergo denitrogenation to
generate carbene species 2, which cyclopropanate styrenes
stereoselectively [Figure 1, (a)].10a Resonance stabilization of
the carbene species by the phthalimido substituent seems to
promote extrusion of molecular nitrogen.13 On the other hand,
5-diethylamino-1-sulfonyl-1,2,3-triazoles 4 are less stable
than the corresponding α-diazo imines. The dominant ring-
opened diazo tautomer readily undergoes denitrogenation to
generate carbene species 5. Subsequently, intramolecular
oxygen
migration
follows
to
afford
N-sulfinyl
benozoylamidines 6 [Figure 1, (b)].11 We recently found an
interesting substituent effect of a p-aminophenyl group
located at the C4-position of N-sulfonyl-1,2,3-triazoles.
R
O
N
SO2R
O
N
N
O
N
H
S
CN
(1)
Although
a p-aminophenyl substituent doesn’t donate
H
electrons as strongly as a phthalimido substituent nor shift the
equilibrium of ring-chain tautomerization such as an amino
substituent at the C5-position, it can thermally promote
denitrogenation of the triazole and induce intramolecular
oxygen migration. In this paper, we report that the thermal
reaction of 4-(p-aminophenyl)-1-sulfonyl-1,2,3-triazoles leads
to the formation of N-sulfinyl imine intermediates, which are
further converted into benzoyl cyanides by Cope-type
+
CH3CN, MW
N
N
N
9a
7a R = Me
7a R = Me
7a R = Me
8a 67% (NMR)
8a 0%
8a 0%
18% (NMR)
90%
80 °C, 10 min
80 °C, 4 h
93%
120 °C, 10 min
120 °C, 10 min
7b R = p-Tol
8b 0%
83%

2
exclusive product. This observation indicated that 8a was
initially produced from the triazole 7a, and underwent further
thermolysis to yield 9a. When the thermal reaction was
carried out at 120 °C for 10 min, 9a was produced in 93%
yield. An analogous thermal reaction of 1-tosyl-substituted
triazole 7b at 120 °C also gave the same cyanide 9a in 83%
yield.
Table 1. Thermolysis of Various 4-(p-Aminophenyl)-1-
mesyl-1,2,3-triazoles 7a
N
SO2Me
O
N
N
CH3CN, 120 °C
10 min, MW
Ar
CN
Ar
H
7
9
O
O
O
The mechanism depicted in Scheme 1 is proposed for the
formation of the cyanide 9a from the triazole 7a. Ring-chain
tautomerization of 7a generates α-diazo imine 10,4 which then
undergoes extrusion of molecular nitrogen with electron-
donating assistance of the p-amino group to afford the
CN
CN
Ph
CN
Ph
N
N
N
Ph
Ph
9d 77%b
resonance-stabilized
carbene
intermediate
(11–13).13
9b 87%
9c 83%
Intramolecular addition of the oxygen atom of the sulfonyl
group to the electrophilic carbon atom furnishes the five-
membered cyclic intermediate 14.11 It is assumed that this
process is also facilitated by the contribution of the resonance
form 13. The O–S bond of 14 is subsequently cleaved to yield
the N-sulfinyl imine 8a. Since the imino carbon possesses a
hydrogen atom, the Cope-type elimination of the sulfinyl
group follows to afford the 4-aminobenzoyl cyanide 9a.14
O
O
O
CN
CN
CN
N
N
N
O
9e 85%
9f 88%
9g 86%
O
O
O
CN
CN
CN
N
N
N
N
N
N
SO2Me
SO2Me
N
N
N
N
Me
Me
9h 90%
9i 77%
9j 38%
H
H
aConditions: 7 (0.50 mmol) was heated in CH3CN (5 mL) at 120 °C
for 10 min under microwave irradiation. Isolated yield. CH3CN (20
–N2
b
N
N
7a
10
SO2Me
mL).
O
triazole was sluggish to give the indole-5-carbonyl cyanide in
38% yield due to the lower electron-donating character of the
nitrogen atom.
SO2Me
Me
S
N
N
N
O
H
H
H
A sequential one-pot procedure starting from terminal
alkynes was carried out to demonstrate the practical
convenience of the present method (Eq 2). Initially, a mixture
of the terminal alkyne (15, 1.0 equiv), mesyl azide (1.0 equiv),
Cu(OAc)2·H2O (5.0 mol %), and 2-aminophenol (2.5 mol %)
in acetonitrile was stirred at room temperature for 4 h to form
N
N
11
12
N
13
O
Me
Me
O
S
O
N S
O
N
CN
O
4-(p-aminophenyl)-1-mesyl-1,2,3-triazoles
7a.
Then,
H
H
–
acetonitrile was added to the same reaction vessel, which was
heated at 120 °C under microwave irradiation for 10 min. The
benzoyl cyanide 9a was isolated in 74% overall yield.
OH
S
N
Me
N
N
9a
8a
14
Scheme 1. Proposed Mechanism for the Formation of 9a
1) MeSO2N3 (1.0 equiv)
H
Cu(OAc)2•H2O (5.0 mol %)
2-Aminophenol (2.5 mol %)
CH3CN (2 M), rt, 4 h
O
The intermolecular cyclopropanation reaction of styrene
(5 equiv) with 7a was attempted (DCE, 55 °C, 12 h) in order
to compare with 4-phthalimido-1-mesyl-1,2,3-triazoles 1.10a
However, only the N-sulfinyl imine 8a (16% NMR yield) and
the benzoyl cyanide 9a (71% NMR yield) were formed, and
no cyclopropane product was obtained. Thus, the carbene
species (11–13) generated from 7a favors the intramolecular
oxygen migration over an intermolecular cyclopropanation
reaction unlike that generated from 1. We assume that this
difference might be ascribed to the contribution of the
resonance form 13 having p-quinoid moiety.
A variety of 4-(p-aminophenyl)-1-mesyl-1,2,3-triazoles
participated in the thermal reaction to give the corresponding
benzoyl cyanides 9b–h in yields ranging from 77% to 90%
(Table 1). The triazole possessing a 2-aminopyridyl group
was also transformed into the 6-aminonicotinoyl cyanide 9i in
77% yield. However, the reaction of 5-indolyl-substituted
CN
(2)
2) CH3CN (0.1 M), 120 °C
10 min, MW
N
N
15
9a 74%
In summary, we have disclosed that the reactivity of N-
sulfonyl-1,2,3-triazoles is significantly affected by the p-
amino substituent on the phenyl group at the C4-position. The
one-pot sequential reaction starting from the terminal alkyne
15 provides a unique example in which the terminal carbon
atom of an alkyne and the nitrogen atom of sulfonyl azide
constitute a cyano functionality of the product.15
This work was supported in part by a Grant-in-Aid for
Scientific Research (B) from MEXT and the ACT-C program
of the JST. Y.F. thanks the JSPS for Yong Scientists for a
Research Fellowship.

3
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12
13
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