A new synthetic route to aryl hydroxysulfonamides via a novel Fries-type rearrangement of aryl N,N-dialkylsulfamates

Article abstract of DOI:10.1016/S0040-4039(01)01893-7

A novel thia-Fries rearrangement of sulfamates 1 in AlCl₃ giving good yields of para-2 and ortho-3 arylhydroxysulfonamides offers a new and efficient route to these sulfonamides.

Full text of DOI:10.1016/S0040-4039(01)01893-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8729–8731
A new synthetic route to aryl hydroxysulfonamides via a novel
Fries-type rearrangement of aryl N,N-dialkylsulfamates
G. Anthony Benson,a,† Patrick J. Maughan,a,* Declan P. Shellya and William J. Spillaneb,*
aDepartment of Applied Sciences, School of Science, Institute of Technology Sligo, Ballinode, Sligo, Ireland
bChemistry Department, National University of Ireland, Galway, Ireland
Received 3 August 2001; revised 17 September 2001; accepted 5 October 2001
Abstract—A novel thia-Fries rearrangement of sulfamates 1 in AlCl3 giving good yields of para-2 and ortho-3 arylhydroxysulfon-
amides offers a new and efficient route to these sulfonamides. © 2001 Elsevier Science Ltd. All rights reserved.
In this communication, we report a novel thia-Fries
rearrangement (Scheme 1) in which a series of ten aryl
N,N-dialkylsulfamates 1 have been isomerised to para-
2 and/or ortho-3-hydroxysulfonamides in good yields
(Table 1). This is a new and efficient method for
When 2,4,6-trichlorophenyl N,N-dimethylsulfamate
was subjected to the rearrangement conditions it did
not react and no trace of the meta-hydroxysulfonamide
was found. Where comparison is possible, yields of
sulfonamide product(s) in this present rearrangement
are comparable to or generally better than those
reported in alternative syntheses.3–9 Further, the rear-
rangement appears to offer a short and convenient
route to sulfonamides from certain medicinally impor-
tant steroidal sulfamate esters.10
synthesising
sulfonamides
bearing
an
-OH
functionality.
Since the original report of Rittler1 of the Fries rear-
rangement giving hydroxydiarylsulfones, there have
been numerous literature references to this
rearrangement2a–d and the majority of these deal with
the rearrangement of arylsulfonates, PhSO2OPh to sul-
fones, HOC6H4SO2Ph.
The ortho/para ratio in the rearrangement has been
explored for 1 (R1=R2=Me) under varying conditions
(Table 2). Shorter reaction times and lower tempera-
tures seem to favour the ortho-isomer; at temperatures
of ]120°C the ortho/para ratio is fairly constant except
at 140°C when it is maximised after 10–15 min of
reaction We have established that the two sulfonamides
isolated are very stable and do not rearrange when
heated over a range of 60–150°C in AlCl3. An almost
quantitative product balance was achieved between
In Table 1 in runs 1–3 good yields of ortho- and
para-sulfonamides were obtained. In runs 4 and 6–9,
where the para-position is blocked, only ortho-sulfon-
amide product was obtained. In runs 5 and 10 (both
ortho-positions are blocked) only para-sulfonamide
product was recovered.
Scheme 1.
* Corresponding authors. E-mail: maughanp@eircom.net; william.spillane@nuigalway.ie
† Deceased.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01893-7

8730
G. A. Benson et al. / Tetrahedron Letters 42 (2001) 8729–8731
Table 2. ortho/para Ratio obtained in the rearrangementa
of sulfamate ester 1 (R1=R2=Me) in AlCl3 at various
temperatures and times
Table 1. Rearrangementa of sulfamate esters to arylhy-
droxysulfonamides in AlCl3 at 140°C for 1 h
Temp. (°C)
ortho/para
Time (min)
5
10
15
30
60
90
100
110
120
130
140
2.7
1.2
1.2
0.6
0.5
0.5
1.3
1.2
1.1
0.6
0.5
1.0
1.1
0.8
0.6
0.5
0.5
0.9
1.3
0.9
0.7
0.4
0.5
0.5
0.7
0.7
0.6
0.5
0.5
0.5
a Using 0.5 g ester and a 1:1 molar ratio of ester to AlCl3. The
various temperatures ( 5°C) were maintained in an oil bath.
Detection of isomers was by reversed-phase HPLC.
ester and product(s) though at higher temperatures
some decomposition to parent phenol (510%) was
noted.
Crossover experiments to explore the molecularity of
the rearrangement are in hand using nitrobenzene as
solvent. Further work is in progress to maximise
yields, to probe other effects, e.g. varying catalyst,
solvent etc. and to attempt the rearrangement of
sulfamates of the type ArOSO2NH2 which, if success-
ful, could provide a route to many medicinally impor-
tant sulfonamides.
a Using 0.5 g ester and a 1:1 molar ratio of ester to AlCl3. An oil bath
at 140 5°C was used for the reaction. The reaction was quenched
with HCl and after extraction with CH2Cl2 product(s) were sepa-
rated by column chromatography (silica gel) or by distillation under
reduced pressure. b These were prepared by a standard method
involving reaction of the appropriate sulfamoyl halide with the
appropriate phenol giving generally ꢀ70% yields. All gave good C,
H and N microanalysis (within 0.5%) except the sulfamate used in
run 9 which had % C 38.96 (found); requires 39.52%. 1H and 13C
NMR and MS were obtained for all esters. Esters used in runs 1, 4,
7, and 8 and the 2,4,6-trichloro ester (Ref. 4) and in run 2 (Ref. 5)
have been reported previously and the mp’s/bp’s obtained are in
agreement with reported values. c The sulfonamides all gave C, H
and N microanalysis (within 0.5%) except the products in run 7,
which had % C 50.23 (found); requires 51.58% and % N 6.51,
requires 5.96% and in run 9 which had % C 38.96 (found); requires
39.93%. 1H and 13C NMR and MS were obtained for all thirteen
sulfonamides prepared. d The ortho/para ratio is given in parenthe-
ses for runs 1–3. e The ortho-hydroxy compound, mp 91–92°C (lit.6
67–70°C) was synthesised by an alternative route by us and gave a
material with mp 91–92.5°C. The MS of the two compounds made
by us were identical. The para-hydroxy compound had a mp of
97–98°C (lit.7 95°C; lit.8 94°C; lit.9 95–96°C). f The para-hydroxy
compound, mp 94.5–95.5°C (lit.6 68–70°C; lit.10 49–50°C) was syn-
thesised by an alternative route by us and gave a material with mp
94.5–95.5°C. The MS of the two compounds made by us were
identical. g The para-hydroxy compound had a mp of 100–102°C
(lit.6 102–104°C). h The product shown mp 162–165°C (lit.11 160–
165°C; lit.12 137–138°C) gave 1H and 13C NMR and MS spectra
which were consistent with the structure shown.

G. A. Benson et al. / Tetrahedron Letters 42 (2001) 8729–8731
8731
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