Aminosulfonylation of aromatic amines, sulfur dioxide and hydrazines

Article abstract of DOI:10.1039/c4cc03032j

A facile route to aryl N-aminosulfonamides under mild conditions is provided. The reaction of aromatic amines (including heteroaromatic amines), sulfur dioxide, and hydrazines proceeds efficiently with good functional group tolerance. The in situ generated diazonium ion is involved in the aminosulfonylation process. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc03032j

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Aminosulfonylation of aromatic amines, sulfur
dioxide and hydrazines†‡
Danqing Zheng,a Ying Li,a Yuanyuan Ana and Jie Wu*ab
Cite this: Chem. Commun., 2014,
50, 8886
Received 24th April 2014,
Accepted 19th May 2014
DOI: 10.1039/c4cc03032j
www.rsc.org/chemcomm
A facile route to aryl N-aminosulfonamides under mild conditions is alkynes,3b and arylboronic acids3c was successfully achieved.
provided. The reaction of aromatic amines (including heteroaromatic According to the findings, stoichiometric acids including Lewis
amines), sulfur dioxide, and hydrazines proceeds efficiently with acid and protonic acid were crucial for the process, and the in situ
good functional group tolerance. The in situ generated diazonium generated diazonium ion was shown to be the key intermediate.
ion is involved in the aminosulfonylation process.
As an emerging technique, a continuous-flow technique was
successfully employed by Buchwald and co-workers in the direct
Aromatic amines are a type of readily available and abundant organic Wagner-Meerwein-type arylation of vinyl ether using aromatic
synthon either in transition metal-catalyzed coupling reactions or amines as the aryl group donors.4 Further important progress
non-metal-mediated transformations, as represented by the Ullmann involving copper- and silver-mediated Sandmeyer trifluoromethyla-
reaction and the Buchwald–Hartwig coupling reaction. During the tion of aromatic amines, was reported by Wang and Fu.5 Direct
past century, these thriving achievements in the realm of transition Sandmeyer-type borylation and stannylation of aromatic amines
metal-catalyzed (especially copper and palladium) C–N coupling was subsequently accomplished.6
reactions, have been witnessed.1 However, enough emphasis has
On the other hand, aminosulfonylation has been utilized as
not been put on the transformations involving the free amino group an efficient approach for the generation of sulfonamides, which
of aromatic amines as a formal leaving group, in part probably are widespread in drugs and natural products.7 Although direct
because of the relatively inert nature of the C–N bond in aromatic amination of sulfonyl chlorides with amines could afford the
amines. It’s generally accepted that conversion of the C–N bonds in corresponding sulfonamides, much attention has been paid to the
aromatic amines into carbon–carbon bonds and carbon–heteroatom insertion of sulfur dioxide8,9 for the preparation of sulfonamides. So
bonds represents a significant and attractive strategy due to the far, aryl halides, arylboronic acids, as well as aryldiazonium tetra-
aromatic amines’ easy accessibility, low-toxicity, relatively high fluoroborates, have been used in the coupling of sulfur dioxide with
stability, and applicability in numerous transformations.2a,b One hydrazines. Sources of sulfur dioxide include DABCO-bis(sulfur
initially elegant example involving the reaction of an aromatic dioxide) and inorganic metal sulfides. Very recently, we reported
amine with acrylonitrile was developed in 1977 by Doyle and a radical process for the synthesis of N-aminosulfonamides
co-workers.2c In 2013, another copper-catalyzed example was through a reaction of an aryldiazonium salt, DABCOÁ(SO2)2, with
described for the direct arylation of pyrroles and benzoquinone hydrazines.9c As mentioned above, during the coupling of aromatic
via C–H activation using aromatic amines as the aryl source.2d,e amines, the in situ generated diazonium ion was identified as the
Palladium-catalyzed direct arylation using aryl amines as the aryl key intermediate. We therefore envisioned that aromatic amines
source was also developed,3 and direct arylation of styrene,3a,d,e might also be utilized as the substrate in the insertion reaction of
sulfur dioxide.
As a source of sulfur dioxide, DABCOÁ(SO2)2 is stable and easy
a Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433,
to handle, therefore, we initially studied the transformation of
China. E-mail: jie_wu@fudan.edu.cn; Fax: +86 21 6564 1740;
p-toluidine 1a in the reaction of DABCOÁ(SO2)2 and morpholin-4-
Tel: +86 21 6510 2412
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032,
China
amine 2a (Table 1). We began our exploration with the addition
of HBF4 and tBuONO. To our delight, the desired product 3a was
obtained in 33% yield (Table 1, entry 1). The reaction proceeded
very fast within 15 min. This exciting result encouraged us to
undertake further investigations. The yield was higher when
the amount of acid was increased (Table 1, entries 2 and 3).
† Dedicated to Prof. Li-Xin Dai on the occasion of his 90th birthday.
‡ Electronic supplementary information (ESI) available: Experimental procedure,
characterization data, and 1H & 13C NMR spectra of compound 3. See DOI:
10.1039/c4cc03032j
8886 | Chem. Commun., 2014, 50, 8886--8888
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1
Optimizing conditions for the reaction of p-toluidine 1a,
Table 2 Scope investigation for the aminosulfonylation reaction of anilines 1,
DABCOÁ(SO2)2 and hydrazines 2a
DABCOÁ(SO2)2, and morpholin-4-amine 2aa
Molecular ratio
Entry
Additive
(1a/tBuONO/additive/2a)
T (1C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
HBF4
HBF4
HBF4
HCl
CF3SO3H
CH3SO3H
CH3CO2H
BF3ÁOEt2
BF3ÁOEt2
BF3ÁOEt2
1.2/1.4/2.4/1.0
1.2/1.4/1.4/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
1.5/1.8/1.8/1.0
5
5
5
5
5
5
5
5
30
50
33
40
53
35
45
43
40
64
85
83
a
Reaction conditions: p-toluidine 1a and acid in CH3CN (1.0 mL),
followed by dropwise addition of tBuONO at 0 1C. After 5 min, the above
mixture was slowly added into a mixture of DABCOÁ(SO2)2 (0.18 mmol)
and morpholin-4-amine 2a (0.30 mmol) in CH3CN (3.0 mL), under N2
b
protection at the temperature as indicated in the table. Isolated yield
based on morpholin-4-amine 2a.
No better results were obtained when the acid was changed to HCl,
CF3SO3H, CH3SO3H, or CH3CO2H (Table 1, entries 4–7). Gratifyingly,
when Lewis acid BF3ÁOEt2 was used as a replacement for protonic
acid, the corresponding product 3a was obtained in 64% yield
(Table 1, entry 8). The yield improved (85%) when the reaction
temperature was changed to 30 1C (Table 1, entry 9). A similar result
was observed when the reaction occurred at a higher temperature
(Table 1, entry 10).
a
Isolated yield based on hydrazine 2.
The reaction scope of anilines 1, DABCOÁ(SO2)2, and hydrazines
2 was then explored under the above optimized conditions observed when 2-aminopyridine or 2-aminopyrimidine was
t
(1.8 equiv. of BuONO, 1.8 equiv. of BF3ÁOEt2, MeCN). The results applied in the reaction. For 3-aminopyridine, the reaction only
of the aminosulfonylation are shown in Table 2.10 A range produced a low yield of the corresponding product 5c. Further
of anilines reacted well with DABCOÁ(SO2)2 and the hydrazines, investigation showed that in the case of quinolines and indoles,
leading to the expected aryl N-aminosulfonamide 3 in good to the desired products 5d–5h could be formed in moderate yields.
excellent yields. It was found that different functional groups were These transformations indicate that this new method is an
all compatible under the standard conditions, and the sensitive important supplement to the previous reports,8,9 considering
ester and hydroxy groups all survived during the transformation. the significance of heterocycles.
For instance, the ester-substituted product 3d was afforded in 73%
For the mechanism of the above transformations, it was
yield and the hydroxy-substituted compound 3f was generated in recognized that the aryldiazonium salt would be the key inter-
55% yield. The yields did not show big differences when anilines mediate, and would be generated from aniline in the presence
t
with electron-withdrawing or electron-donating groups on the of BuONO and BF3ÁOEt2.11 The subsequent radical process,
aromatic ring were employed. Additionally, reactions of anilines with the insertion of sulfur dioxide, would produce the expected
bearing ortho-substituents also worked smoothly to give the desired aryl N-aminosulfonamides.9c
products. For example, 2,4,6-trimethylaniline reacted with
In summary, coupling of aromatic amines (including hetero-
DABCOÁ(SO2)2 and morpholin-4-amine 2a and afforded the aromatic amines) with DABCOÁ(SO2)2 and hydrazines under mild
corresponding product 3k in 77% yield. We also examined conditions, leading to aryl N-aminosulfonamides in good to
other hydrazines 2 in the coupling of sulfur dioxide with aniline. excellent yields, has been described. Different functional groups
As expected, not only aliphatic but also aryl hydrazines could be including ester, hydroxyl, chloro, and trifluoromethyl groups are
incorporated well during the reaction process. It is noteworthy that compatible under these conditions. Moreover, some hetero-
all reactions finish in 15 min under mild conditions to generate the aromatic amines proceeded well in this transformation. This
desired aryl N-aminosulfonamides 3.
thriving chemistry involving the formal removal of an amino
The aminosulfonylation of heteroaromatic amines with group from an aromatic amine, represents an alternative aryl
sulfur dioxide and morpholin-4-amine 2a was investigated next source for the insertion of sulfur dioxide. Further exploration of
(Table 3). Unfortunately, no desired products (5a and 5b) were sulfur dioxide insertion is ongoing in our laboratory.
This journal is ©The Royal Society of Chemistry 2014
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3
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10 General experimental procedure for the aminosulfonylation reac-
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(0.54 mmol) was added to a solution of aniline 1 (0.45 mmol) and
BF3ÁEt2O (0.54 mmol) in CH3CN (1.0 mL) dropwisely at 0 1C. After
5 min, the solution was slowly added into a mixture of DABCOÁ
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8888 | Chem. Commun., 2014, 50, 8886--8888
This journal is ©The Royal Society of Chemistry 2014