Tetrahedron Letters
An efficient practical tosylation of phenols, amines, and alcohols
+
À
employing mild reagent [DMAPTs] Cl
⇑
Chiranjeevi Dhonthulachitty, Sridhar Reddy Kothakapu, Chandra Kiran Neella
Dept of 5-yr Integrated Chemistry, Palamuru University, Mahabubnagar, Telangana State 509001, India
a r t i c l e i n f o
a b s t r a c t
+
À
Article history:
Efficient exploration of [DMAPTs] Cl for base free and chromatography free preparation of sulfonate
esters from phenols and alcohols and sulfonamides from amines was achieved in excellent yields.
Majority of the phenols irrespective of their substituents electronic nature underwent tosylation nearly
at same reaction rate with an average yield of 95%. For amines, ring activating substituents favors rapid
sulfonylation while the ring deactivating substituents relatively lowers the rate of tosylation.
Furthermore the reagent was employed for Chemoselective sulfonylation as well as solvent free tosyla-
tion of phenols and amines.
Received 12 August 2016
Revised 31 August 2016
Accepted 3 September 2016
Available online xxxx
Keywords:
+
À
[
DMAPTs] Cl
Ó 2016 Elsevier Ltd. All rights reserved.
Base free tosylation
Sulfonate esters
Sulfonamides
Green reagent
Introduction
diamines as bases for high reaction rates with economic process by
1
3
minimizing side products. Metal catalyzed tosylation using vari-
ous metal catalysts, i.e., Yb(OTf) , Cobalt(II) salts, Bismuth(III)
halides, and Ag O, etc. solved the problem of base sensitivity but
suffered from relatively vigorous reaction conditions with long
Functional group interconversion (FGI) in Organic Chemistry
plays a decisive role for the synthesis of many natural products.
One among them is interconversion of phenols and alcohols into
respective sulfonate esters and amines into sulfonamides. High
biological profile of sulfonamides (privileged structures), such as
anti inflammatory, anti cancer, anti viral, HIV protease inhibitors,
3
1
2
1
4
reaction times leading to lesser yields. Few green protocols by
employing water as solvent and certain solvent free tosylations
procedures were also developed but has gained little attention as
maintenance of pH of the medium and preparation of organic bases
2
,3
anticonvulsant, etc. evolved them into marketed drugs such as
4
5
15
amprenavir as HIV protease inhibitor, sildenafil as phosphodi-
required for tosylation limits their applications. Almost all of the
6
esterase inhibitor, bosentan as anti hypertensive drug, etc. Like
sulfonamides, sulfonic esters also display important pharmacolog-
ical activities. Besides that, though synthetically these tosyl
aforesaid methodologies require either a base/catalyst to promote
tosylation or chromatographic purification to isolate the pure
product. Henceforth, an environmentally benign protocol is still
needed which overcome both the above mentioned setbacks. Here
in we wish to report, in this letter, an eco-friendly tosylation pro-
7
derivatives serve in different ways, masking of many functional
8
9
groups and as alkylating agents under SN reactions are a couple
of fundamental applications in organic chemistry therefore synthe-
sis of sulfonamides and sulfonic esters have attracted many syn-
thetic chemists across the globe.10 The classical tosylation
+
À
cedure employing [DMAPTs] Cl as a green reagent which neither
uses a base nor requires chromatographic purification for effective
tosylation.
1
1
procedure, which involves treatment of a substrate with TsCl
and Py/NEt in DCM, has some setbacks vowing to its longer reac-
3
Results and discussion
tion times which leads to undesired reactions such as disulfon-
amide formation and under some circumstances even functional
group compatibility. Many methods have been progressed to
address these problems. Notably, Tanabe et al. developed several
tosylation pyridine free protocols either by employing organic base
and its hydrochloride salt as base or by using substituted ethylene
+
À16
After successful usage of [DMAPTs] Cl
for the regioselective
1
2
tosylation of ene polyols and for rapid base free quantitative tosy-
1
7
lation of aniline, phenol, and 2-naphthol, we inspired for its fur-
ther exploration on direct tosylation of diverse class of
a
substrates. In this direction, various phenol derivatives and amines
both containing ring activating and deactivating substituents, and
alcohols were tested for tosylation with 1.
⇑
040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
0