Recueil des Travaus Chimiqires des Pays-Bas. l08/1, January 1989
I
Full papers
Recl. Trav. Chim. Pays-Bas 108, 7-13 (1989)
0165-05 13/89/0107-07$2.25
Reactions of the dihydroxybenzenes and their methyl ethers with sulfur trioxide.
The effect of initial sulfation on the sulfonation product distribution"+
Hans Cerfontain*, Norbert J. Coenjaarts and Ankie Koeberg-Telder
Laboratory of Organic Chemistry, University of Amsterdam. Nieuwe Achtergracht 129.
1018 19;s Amsterdam, The Netherlands
(Received June 3rd. 1988)
Abstract. The sulfation and sulfonation resulting from the reaction of the dihydroxybenzenes and
their mono- and dimethyl ethers with SO, in nitromethane have been studied, and their product
distributions are reported. As to the non-hydroxy-substituent-containingsubstrates, 1,2-dirnethoxybenzene (3) yields the 4-sulfonic acid (3-4-S) which, upon further sulfonation, yields a 1:4 mixture
of the 3,5- and 4,5-S,. The 1,3- (6) and 1A-isomer (9) yield initially the 4- and 2-S, respectively, and
subsequently exclusively 6-4,6- and 9-2,5-S,, respectively.
With the substrates containing one hydroxy substituent, the sulfonation isomer distribution is
dependent on the SO, to substrate ratio if the OH and OMe substituents are in ortho or para
orientation, due to increasing sulfonation of the corresponding methoxyphenyl hydrogen sulfate.
Thus, 2-methoxy- ( 2 ) and 4-methoxyphenol (8) with one equiv of SO, at 0 ° C yield a 3: 1 mixture of
2-4-S and 2-5-S and a 9 : l mixture of 8-2-S and 8-3-S, respectively, but, with 2 4 equiv of SO,, the
former reactant yields only 2-5-S and the latter only 8-3-S. 3-Methoxyphenol (5) yields initially a 1: I
mixture of the 4- and 6-sulfonic acid. Further sulfonation yields only 5-0,4,6-S, which slowly cyclizes
to the 1,3,2,4-benzodioxadithiin2,2,4,4-tetraoxide derivative 11.
As to the dihydroxy-containing substrates, 1,2-dihydroxybenzene (1) with 1 equiv of SO, first yields
the hydrogen sulfate 1 - 0 - S which rearranges to 1-4-S; on using an excess of SO,, the eventual
product is 1-0(2),4-S,. Similarly, the 1,4-isomer (7) with 1 equiv of SO, yields initially 7-0-S which
isomerizes to 7-2-S. With 6 equiv of SO,, initially 7-0,O-S, is formed and subsequently its 2-sulfonic
acid, which eventually cyclizes slowly to the 1,3,2,4-benzodioxadithiin2,2,4,4-tetraoxide derivative
12. The 1,3-isomer 4 with 1 equiv of SO, yields the 4-sulfonic acid. With 4 equiv of SO,, initially
4-0,0-S, is formed and subsequently 4-4,O,O-S, , which is converted into both 4-0,0,4,6-S, and
the cyclization product 10. Eventually, small amounts of 4-0,2,4,6-S, and 14-2,6-S, are formed by
transsulfonation.
Introduction
Results
In continuation of our mechanistic studies on the sulfonation of the three dihydroxybenzenes and their methyl ethers
with sulfuric acid as reagent and s o I ~ e n t ~we
- ~ now
,
report
the sulfonation of these substrates by sulfur trioxide in
aprotic solvents. The number of sulfonation studies of
phenolic-type compounds under aprotic reaction conditions
is quite limited5-'. Reaction of phenol with a slightly deficient amount of SO, in nitromethane at - 35°C leads to the
rapid formation of phenyl hydrogen sulfate which, at O'C,
slowly yields phenol-4-sulfonic acid7. The substitutiod patterns on reaction of chloro-', di~hloro-~.',methyL9 and
dimethyl-phenols' with SO, where recently reported; for a
number of reactants, the substitution pattern was found to
depend on the SO,/substrate
The changed substitution pattern observed on using a large excess of SO, was
ascribed to (additional) sulfonation of the aryl hydrogen
sulfate, the reacting substrate on using 1 equiv of SO, or
less being the corresponding phenol itself.
The dihydroxybenzenes and their mono- and dimethyl
ethers 1-9 have been sulfonated with SO, in nitromethane
as solvent in order to study their sulfation and sulfonation.
i
R'=R~=H
4 R'=R2; H
7
R'=R~=H
2
R'=H.R2=Me
5 R'=H.R2=Me
8
R'=H.R2=Me
3
R'=R2=Me
6
R'=R2=Me
9
R'=R2=Me
Aromatic Sulfonation 107. For part 106, see ref. 1.
For reasons of convenience, the aromatic ring positions of the
sulfonic acids and the hydrogen sulfates have been numbered as
for the parent substrate.
8
Hans Cevfontain et al. /Reactions of the dihydroxybenzenes and their methyl ethers
Discussion
Dimethoxybenzenes
10
13
12
11
Reaction of the 1,2-isomer 3 with SO, leads solely to
1,2-dimethoxy-4-sulfonicacid (3-4-S) which, upon further
sulfonation, yields 3-3,5( = 4,6)-S, and 3-43-S, in a ratio of
1 : 4 (cf: Table I). This sulfonation behaviour is quite similar
to that observed on using concentrated sulfuric acid, the
ratio of the two disulfonic acids being then however
10: 14.". The 1,3-isomer 6 with SO, yields (4 Table II), as
observed with concentrated aqueous sulfuric acid3, 6-4-S,
which subsequently yields 6-4,6-S2. The exclusive formation
of the 4-sulfonic acid upon sulfonation of both 1,2- (3) and
1,3-dimethoxybenzene ( 6) with 1 equiv of SO, is in fact
predicted on the basis of the principle of additivity of substituent effects, since the sole product on sulfonation of
anisole with 1 equiv of SO, is the 4-sulfonic acid6.l2.
The 1,4-isomer 9 with SO, yields 9-2-S (cf. Table III),
which, upon further sulfonation with SO,, as with concentrated aqueous sulfuric acid2, yields exclusively 9-2,5-S,.
The absence of any sulfonation at the 6-position is due to
steric hindrance by the I-methoxy methyl which, due to
repulsion by the bulky sulfo group, is pointing towards 6-H.
The effect of the sulfo group in 9-2-S, which is strongly
meta-directing on electronic ground^'^, is apparently overruled by the steric factor.
The reaction mixture product composition for a given substrate has been determined as a function of the relative
amount of SO, used and of the reaction time. The results
for the l,2-, 1,3- and 1,4-disubstituted reactants are compiled in the Tables 1-111, respectively. Demethylation was
not observed to have occurred with any of the studied substrates or their sulfonic acids, although this process was
recently observed on reacting 4-methoxyphenol (8) and its
3-sulfonic acid (8-3-S) with fuming sulfuric acid2. Intramolecular cyclization of a 2-sulfophenyt hydrogen sulfate
moiety to yield the corresponding 1,3,2,4-benzodioxadithiin
2,2,4,4-tetraoxide was observed on reaction of 3-methoxyphenol (5), 1,3- (4) and 1,4-dihydroxybenzene (7) with an
excess of SO, as appears from the eventual presence of 11,
10 and 12, respectively. From the data shown in
Tables 1-111, it appears that the various phenyl .hydrogen
sulfates and the 1,3,2,4-benzodioxadithiin 2,2,4,4-tetraoxides 10-12 are completely hydrolyzed to the corresponding phenols and the o-phenolsulfonic acids, respectively,
upon aqueously working-up the nitromethane reaction mixtures.
With the dimethoxybenzenes 3, 6 and 9, only mono- and
disulfonation are observed. With the methoxyphenols 2, 5
and 8 and the dihydroxybenzenes 1 , 4 and 7, sulfation was
also observed.
Table I
Substrate
Dihydroxybenzenes
The 1,2-isomer 1, upon reaction with SO, ($Table I), will,
as was in fact established for phenol itselp, be sulfated to
yield 1-hydroxy-2-phenyl hydrogen sulfate [1-0(2)-S]
which, on using 1.0 equiv of SO,, will rearrange to 1-4-S".
On using 4.0 equiv of SO,, the eventual product 1-0(2),4-S,
is formed by sulfonation of 1 - 0 - S and/or by rearrangement
of 1-0-S to 1 - 4 3 , and subsequent sulfation which will occur
Reaction of 1.2-dihydroxybenzene (I) and its methyl ethers with SO, in nitromethane at 0°C.
~
Method"
SO,,
equiv
1
Reaction
time (min)
Product composition, %'
Unconverted
substrate (%)"
4- s
0,4-S,
5-s
0,5-S,
3,5-s,
4,5-s,
~
1 .o
4.0
1.o
2
A
A
15
170
24
60
6.0
150
0.9
15
45
1300
4.0
30
8
6
nd
> 98
> 98
26
22
+ +e
++
++
11
-
> 98d
> 98
> 98
I E
0.5
1.o
2.0
4.0
6.0
8.0
4.0
8.0
1 .o
4.0
4.0
60
60
60
60
60
60
60
60
nd
nd
nd
30
30
nd
nd
nd
f
+
+
70
70
30
30
310
B
+=
73
76
40
19
17
19
98
69
9
27
24
60
81
83
81
> 98
> 98
2
26
73
5
18
S stands for SO,H when method A was applied and for SO,- using method
nd stands for not determined.
See Experimental.
The major product is 4-S. ' The reaction mixture was first maintained at 0 ° C for 40 min and then
The product is 1-0(2),4-S,.
B.
at 40°C for a further 40 min.
Method"
4.0
1
.o
4.0
1.o
4.0
0.9
4.0
1.o
4.0
1.o
30
45
18
63
10
45
45
16
30
15
20
35
50
60
70
240
60
60
Reaction
time
(min)
a-c
See the corresponding subscripts of Table I.
of the sulfo product composition.
6
5
4
Substrate
-
-
0-s
0,o-s,
~
-
53
7
-
41
39
42
39
> 98
> 98
> 98
4- s
-
66
63
52
35
23
12
0,0,4-S,
-
13
14
15
15
15
13
7
-
-
48
46
47
41
93
4
> 98
10
11
61
4,6-S,
25
I1
9
18
26
37
0,4,6-S,
Product composition (%
6-S
10
-
-
The assignments of these two structures are tentative with the exception of the 4-2,4,6-S3 moiety.
30'
nd
nd
31
21
nd
-
10
10
(%.)"
Unconv
substr
Table II Reaction of 1,3-dihydroxybenzene (4) and its methyl ethers with S O , in nitromethane at 0°C.
1
2
2
+
Calculated on the basis
16
21
31
41
44
46
50
1
3
91
89
15
78
80
83
85
87
88
89
90
Hans Cefontain et al. /Reactions of the dihydroxybenzenes and their methyl ethers
10
100-
0s
05
on
OH
"1.
80.
60
LO
10-2.6-51
10
Scheme 1 . Reaction of 1.3-dihydroxybenzene (4) with 4 . 0
equiv of SO, in nitromethane at 0' C.
10
0
m
20
60
160
'
220
R P O C ' I O ~l i m e I min I
Fig. I. Reaction of 1,3-dihydroxybenzene (4) with 4.0 equiv
of SO, in CZH,NO, at 0°C. S stands f o r S 0 , H . x
4-0.2,4,6-S4; V : 10-2,6-S,.
at O(2) because of specific conjugative electron release
from the 1-OH to the 4-sulfo group.
The 1,3-isomer 4 with 1.0 equiv of SO, yields exclusively
4-4-S (cf: Table II), presumably (vide supra) via the hydrogen
sulfate 4-0-S as intermediate. The product composition as
a function of the reaction time using 4.0 equiv of SO, is
shown in Fig. 1. The observed initial product is the disulfated species 4-0,O-S, (cf: Scheme 1) which subsequently
yields 4-0,0,4-S,, most likely by direct sulfonation of
4-0,O-S,. The entity 4-0,0,4-S, then undergoes both ring
closure to the sulfated 1,3,2,4-benzodioxadithiin2,2,4,4-
-tetraoxide derivative 10 and sulfonation to 4-0,0,4,6-S,.
In the later stages, further ring sulfonation takes place yielding derivatives of 4-2,4,6-S,, e.g. 4-0,2,4,6-S, and
10-2,6-S,. The required additional SO, is furnished by the
0-desulfonation of 4-0,0,4,6-S,.
The 1,4-isomer 7 with 1.0 equiv of SO, initially yields predominantly 4-hydroxyphenyl hydrogen sulfate (7-0-S) and a
very small amount of the disulfated species 7-0,O-S, (cf:
Table 111). Subsequent rearrangement of 7-0-S yields16
7-2-S relatively slowly. With 6.0 equiv of SO,, the initially
observed product is 7-0,O-S, which is sulfonated to yield
7-0,0,2-S, which very slowly cyclizes to the 1,3,2,4-benzodioxadithiin 2,2,4,4-tetraoxide derivative 12.
Methoxyphenols
2-Methoxyphenol (2) with 1.0 equivalent or less of SO,
yields the 4- and 5-sulfonic acid in ratio of 75 : 25, whereas
this ratio is <0.02 on addition of the substrate to 4-8 equiv
of SO, (6Table I). This variation may be explained. in
Table 111 Reaction of 1.4-dihydroxybenzene (7) and its methyl ethers with S O , in nitromethane.
Substrate
Method"
so,
t
equiv
Temp
("C)
Reaction
time
(min)
Unconv
substr
(%I"
Product composition (%)'
-
0-s
0.0-s2 2-s
0,0,2-s,
3-s
0,3-S2
~
A
A
A
a-C
1 .o
2.5
6.0
20
25
20
B
B
B
1 .o
6.0
6.0
20
20
45
A
0.9
0
A
B
B
B
B
B
B
4.0
I .5
1.5
1.5
1.5
1.5
4.0
0
0
12
25
35
45
0
60
60
60
60
60
45
B
B
1 .o
4.0
0
0
60
60
12
240
45d
12d
30
65
23
11
10
56
30
44
75
57
25
43
> 98
> 98
> 98
21
21
7
7
nd
nd
nd
nd
nd
8
9
16
36
38
92
91
84
64
62
> 98
nd
nd
> 98
5
3
2,5-S,
4
65
65
41'
10
See the corresponding subscripts of Table I.
2H,0. ' Molar composition!
96
70
35
66
10
2700
10000
10000
15
26
2700
9900
20
90
300
12
-
4
-
This datum may be too low
96
a result of the relatively low solubility of 7 in
11
Reciieil des Travau.\- Chimiques des Pays-Bas, 10811, January 1989
terms of the nature of the substrate species being sulfonated. Upon addition of SO, to a phenol, initially the
sulfation equilibrium is readily set up. The sulfonic acids
may then be formed from the corresponding phenyl hydrogen sulfate via two routes:
ROC,H,OH
ROC,H,OH
ROC,H,OSO,H
+ SO,
+ SO,
+ SO,
ROC,H,(SO,H)OSO,H
R
=
=$
ROC,H,OSO,H
(1)
I ,3,2,4-Benzodioxadithiin
2,2,4,4-tetroxides
+
ROC,H,(SO,H)OH
(2)
+
ROC,H,(SO,H)OSO,H
(3)
Reaction of the hydroxy-containing reactants 4, 5 and 7
with a large excess of SO, leads eventually to the formation
of substantial amounts of the 1,3,2,4-benzodioxadithiin
2,2,4,4-tetraoxides 10, 11 and 12, respectively. These
compounds are formed by intramolecular cyclization of the
corresponding 2-sulfophenyl hydrogen sulfate, as proposed
in Scheme2.
S ROC,H,(SO,H)OH
+ SO,
(4)
Me, H
first by regeneration of SO, and the phenol followed by ring
sulfonation (steps .- 1 and 2) and second by initial C-sulfonation (step 3) and subsequent 0-desulfonation (step 4).
The isomer ratio on using a deficient amount of SO, will be
the result of sulfonation of the 2-methoxyphenol proper,
whereas that observed on using a large excess of SO, is that
of sulfonation of 2-methoxyphenyl hydrogen sulfate. Evidence in favour of this proposition is provided by the
observation that 2-methoxyphenyl methanesulfonate, which
is a model compound for 2-methoxyphenyl hydrogen sulfate, yields only the 5-sulfonic acid upon sulfonation with
SO,'.''. The absence of further ring sulfonation upon using
4-8 equiv of SO, also illustrates that 2-4-S and 2-5-S are
fully present as their hydrogen sulfates.
3-Methoxyphenol (5)yields the 4- and 6-sulfonic acid in a
1: 1 ratio (cf: Table 11). Further sulfonation yields the
4,6-disulfonic acid. On using 4.0 equiv of SO,, its hydrogen
sulfate (5-0,4,6-S,) is formed which is converted in part
into the sulfate sulfonate anhydride 11.
4-Methoxyphenol(8) with 1.0 equiv or less of SO, yields the
hydrogen sulfate (8-0-S) which rearranges in part to a mixture of 8-2-S and 8 - 3 4 of which the former predominates
(cf: Table 111). With 4.0 equiv of SO, only products containing the sulfo group at the 3-position are obtained, viz.
8-0,3-S2 and the cyclic dimeric di(su1fonate sulfate)
anhydride 13. The absence of any sulfonation at position 2
may be explained in terms of 4-methoxyphenyl hydrogen
sulfate being the substrate species effectively undergoing
sulfonation. The ratio of [8-2-S]/[8-3-S] is strongly dependent on the relative amount of SO, which is ascribed to the
sulfation equilibrium. From a related study on 2,6-dichlorophenol with SO, in nitromethane', it was concluded that
the sulfation is rapid relative to the ring sulfonation of both
the phenol ( k , k 2 ) and its phenyl hydrogen sulfate
( k , k,). The observed variation in the [8-2-S]/[8-3-S] ratio
with the reaction temperature on using 1.5 equiv of SO,
[from 0.09 at 0°C to 0.6 at 45'C (cf: Table III)] is ascribed
mainly to the temperature dependence of the sulfation
equilibrium. The observed stability of phenyl hydrogen sulfate towards isomerization to phenol-4-sulfonic acid at temperatures below - 15"C6 also demonstrates that the
0-desulfonation step ( - 1) is endothermic and that the
reverse sulfonation step (1) is accordingly exothermic.
+
With 3-methoxyphenol (S), the degree of disulfonation on
using 1.0 equiv of SO, is far less than with 6, and with
1,3-dihydroxybenzene (4) it is absent (Cf. Table 11), which is
the trend to be expected on the basis of the initial sulfation
of 5 and 4.
+
Reactivity of the I .3-isomers
The reactivity for ring sulfonation is very much higher for
1,3-dimethoxybenzene (6) than for the corresponding 1,2(3) and 1,4-isomer (9). This appears from the formation of
33% of 6-4,6-S, in addition to 37% of 6 - 4 4 on using 1.0
equiv of SO,, especially since the SO, reagent was added to
the substrate. The formation of the disulfonic acid may be
ascribed to the very high reactivity of both the substrate 6
and its 4-sulfonic acid, since the intermolecular selectivity
will then be disguised by the rate of mixing of the reagents'".
0'02
HS04
OH
HSO,
Scheme 2. Mechanisms for the I , 3,2,4-benzodioxadithiin
2,2,4,4-tetraoxide formation.
Experimental
The substrates were obtained commercially. The 'H NMR spectra
were recorded on a Varian XL-100-12 and on Bruker AC-200 and
WM-250 spectrometers.
Sulfonation Procedures and Analysis
To a solution of the substrate (0.50 mmol) in [2H,]nitromethane (1.00 ml) was added from a syringe at 0°C under an
atmosphere of N, the desired amount of SO3 and, at appropriately
chosen time intervals, 'H NMR spectra were recorded at 0°C or
at 30°C (the NMR probe temperature).
B. To a solution of the substrate (1.00 mmol) in nitromethane
(7.0 ml) was added over 5 min a solution of the desired amount of
SO, in nitromethane (7.0 ml) at a given temperature (usually 0°C).
After the desired reaction time, 1.0 ml of *H,O was added and the
mixture heated at 40-60" C to hydrolize most of the hydrogen
sulfates and anhydrides. The aqueous layer was isolated and
extracted at room temperature three times with CH,CI, (1-2 ml)
to remove any unreacted substrate and remaining solvent. Residual
CH,CI, was removed by bubbling N, through the aqueous solution
for 30 min. In order to obtain the product analysis, an 'H NMR
spectrum was then recorded. In some cases, the *H,O solution of
the sulfonic acids was neutralized with dilute aqueous potassium
hydroxide, the solvent removed by freeze-drying and an 'H NMR
spectrum of the solution of the remaining potassium sulfonates
dissolved in 'H,O was recorded.
C . This procedure is identical to B except for the method of
mixing the reagents, in that the solution of the substrate in nitromethane was slowly added to the solution of SO, in nitromethane.
The assignments of the products in the (reaction) mixtures were
made on the basis of the observed chemical shifts, absorption area
A.
12
Hans Cerfontain et al. / Reactions of the dihydroxybetizetle.~litid their methyl ethers
Table I V
' H N M R data of 1-9 and their suIfo derivatives
Reactant
Benzene substituents'
Solventb
1
1 J-(HO)2
1,2-(HO),-4-S
1-HO-2-SO-4-S
1-HO-2-Me0
1-HO-2-Me0-4-S
2
-
-5-s
I ,2-( MeO),-3-S
-4-s
-33-s,
-434,
W
W
W
W
1,3-(HO)Z
1,3-(HO)2-4-S
N
N
W
W
N
6.42
6.53
6.84'
7.07
7.50
N
N
N
N
N
1.5
7.83
7.75
8.22
I-SO-2-Me0
1-SO-2-Me0-4-S
-4,6-S,
I-HO-3-SO-4,6-S,
1-H0-3-SO-2,4,6-S3'
I-SO-2,6-S2-3,4-OS0,0S0,-f
1,3-(SO),
1,3-(S0),-4-S'
I - s o - 3 , 4 - o s o 2 0 s o , - (10)g
1,3-(S0)2-4,6-S,
3.91
4.02
4.29
4.02
4.23
3.8
4.12
4.16
4.27
4.27
4.38
4.33
4.37
4.2 1
4.38
4.33
7.46
7.80
7.15
7.37
7.43
7.76
7.88
7.44
8.12
7.77
6.46
W
I-SO-3Me0
1-SO-3-Me0-4,6-S2
3-Me0-4-S-1 ,6-0SO,0SO2- (11)
N
N
N
7.52
7.60
4.28
4.25
1,3-(Me0),-4-S
-4,6-S,
W
W
7.06
7.25
4.32
1,4-(~0),
I-HO-4-SO
1,4-(SO),
1 -HO-4-SO-2-S
1,4-(SO),-S
1-so-3,4-oso,oso,- (12)
W
N
W
N
N
N
N
1-HO-4-Me0
1-HO-4-Me0-2-S
N
N
-3-s
N
W
N
N
N
N
7.27
6.97
7.35
7.61
3.82
3.99
4.22
3.90
4.02
4.06
4.33
I-SO-4-Me0
1-SO-4-Me0-3-S
13
W
W
6.54
6.67
6.87
7.84
5.21
5.12
7.36
7.72
7.35
7.96
7.75
4.26
4.39
7.07
7.37
7.46
7.80
7.52
7.83
8.09
7.84
7.37
8.08
8.05
7.13
7.66
7.95'
8.52
8.43
8.5 1
8.6
6.46
6.60
6.84
8.25
8.36
8.64
7.67
7.83
7.20
7.69
8.0
7.72
8.0
8.22
8.62
7.38
8.62
8.47
6.54
6.67
6.87
8.13
8.63
6.99
7.30
7.65
W
-2,X-S,'
7.5 1
7.76
8.05
-4,6-S,
4.24
4.44
1
8.27
6.48
6.62
6.9'
6.62
6.9'
6.82
7.19
-6-S
6
I
N
N
W
N
W
N
I-HO-3-Me0
1-HO-3-Me0-4-S
5
4
N
N
W
N
N
N
W
N
W
N
N
N
-5-s
3
7.03
3.79
3.98
1.16
1.07
1.25
1.44
3.87
1.15
1.00
7.77
3.04
7.67
8.07
7.96h
<I
7.39'
(AB)
7.47
7.35
7.25
7.85
) 7.96h
7.39'
7.85
7.82
1.13
S stands for S 0 3 H (using C2H,N0, as solvent) and SO3- (using 'H,O).
N and W stand for C2H3N0, and 'H,O, respectively.
The chemical shifts are relative to external neat TMS (capillary); for 'H,O as solvent, the chemical shiR is somewhat dependent
on the acidity.
All the doublets resulting from ortho- and meta-hydrogen coupling have J values of 8-9 and 1.5 Hz, respectively.
The
intensity of the signal is reduced as a result of 'H/H exchange.
The assignments of the structures containing the 4-2,4,6-S, moiety are
tentative.
8 The structural assignments of4-1,3-(SO),-4-S and 10 may be reversed.
h-k The two hydrogens exhibit an AB type of system
which almost resembles a singlet. ' x = 5 or 6.
a
13
Recueil des Travaux Chiniiques des Pays-Bas, 10811, January 1989
ratios and coupling constants in combination with the shielding
parameters of the OH, OMe, SO,-, SO,H, O S 0 , - and
OS0,H“.21-22 substituents. The assignments are compiled in
Table IV. The compositions of the product mixtures were determined by ‘H NMR multicomponent analysis on the basis of the
specific absorptions of the various components“.
Acknowledgements
The authors gratefully thank Mmes N . E . Vreem-Bruinzeel
and H . van der Laan-Ctvrteckova for recording the NMR
spectra.
References and Notes
I
’
’
P. de Wit, A . F. Woldhuis and H . Cefontain, Recl. Trav. Chim.
Pays-Bas 107, 668 (1988).
H. Cerjontain and A . Koeberg-Telder, Recl. Trav. Chim.
Pays-Bas 107, 583 (1988).
H . Cefontain and A . Koeberg-Telder, Recl. Trav. Chim.
Pays-Bas 107, 543 (1988).
H. Cerfontain, N . J . Coenjaarts and A . Koeberg-Telder, Recl.
Trav. Chim. Pays-Bas 107, 325 (1988).
C. M . Suter, P . B . Evans and J . M . Kiefer, J. Am. Chem. SOC.60,
538 1938).
H. Cefontain, “Mechanistic aspects in aromatic sulfonation and
desulfonation”, Interscience publishers, New York, 1968,
pp. 95-1 00; E . E. Gilbert, “Sulfonation and related reactions”,
Interscience publishers, New York, 1965, p. 80.
H . Cerjbntain, A . Koeberg-Telder, H . J . A . Lambrechts and P . de
Wit, J. Org. Chem. 49, 4917 (1984).
P . de Wit and H . Cerjbntain, Recl. Trav. Chim. Pays-Bas 107,
121 (1988).
H . D . Goossens, H . J . A . Lambrechts, H . Cefontain and P . de
Wit, Red. Trav. Chim. Pays-Bas 107, 426 (1988).
The f661fs partial rate factor ratio for the sulfonation of 3 - 4 4 is
very significantly smaller for SO, than for 96.5-98.5% H2S04
as reagent, viz. 0.25 (4 Table I) versus 2
This difference in
the f6/f5 ratio is in line with the difference in the Meofo/Meof,
ratio, the data for SO3 and concentrated aqueous sulfuric acid
being I0.02’ and 0.57”, respectively.
H . Cefontain, H . J . A . Lambrechts, Z . R . H . SchaasbergNienhuis, R . G . Coombes, P . Hadjigeorgiou and G . P . Tucker, J.
Chem. SOC.Perkin Trans. I1 659 (1985).
I’
In contrast, using 98.4% H,S04 instead of SO, as reagent, the
sulfonation of anisole yields both the 0- and p-sulfonic acid in a
ratio of 0.56”, but again 1,2-dimethoxybenzene (3) then yields
only the 4-sulfonic acid4. The absence of any 3-3-S is due to the
fact that 3 is present very predominantly in the anti-anti conformation, since 1,2-(dimethylidenedioxy)benzene,which is a model
compound for the syn-syn conformer of 3, again yields both the
3- and 4-sulfonic acid, viz. in a ratio of 0.82’3.
I’ H . R . W . Ansink, H . Cefontain and A . F. Woldhuis, Recl. Trav.
Chim. Pays-Bas, in preparation.
l 4 A . J . Prinsen, A . Koeberg-Telder and H. Cefontain, Tetrahedron
26, 1953 (1970); H. Ce$ontain, J . Org. Chem. 47, 4680 (1982).
I s The absence of any 1-3-S is in line with the absence of any
2-sulfonic acid in the reaction of phenol with SO,6.
As appears from the data of Tables 1-111 and the data on
phenyl hydrogen sulfate’, the rate of formation of the monosulfonic acid from the corresponding phenyl hydrogen sulfate is
very much smaller for 7 than for I , 4 and phenol, as is in fact
expected on the basis of the (almost) exclusive formation of the
4-sulfonic acid on reaction of phenol with one equiv. of SO,9.
The formation of 18% of 2-4-S upon reaction of 2 with 4-8
equiv of SO, by addition of the latter to the former (method B ,
CJ Table I ) is thought to be the result of adding the SO, to the
substrate. As was shown by Ansink of our laboratory’8, the
inverse mode of addition (method C) in fact leads only to the
formation of the 5-sulfonic acid (cJ Table I). The structural
assignments of the 2-4- and 2-5-sulfonic acids were determined
unambiguously on the basis of NOE difference experiments,
using the multiple irradiation technique”.
I X H. R. W . Ansink, private communication.
I’
D . Neuhaus, J. Magn. Res. 53, 109 (1983); M . Kinns and
J . K . M . Sanders, ibid. 56, 5 I8 (1984).
2o P. Rys, Acc. Chem. Res. 9, 345 (1976); Angew. Chem. 16, 847
(1 977).
‘I
H . Cefontain, A . Koeberg-Telder, C. Kruk and C . Ris, Anal.
Chem. 46, 72 (1974).
M . Hesse, H . Meier and B . Zeeh, “Spectroskopische Methoden
in der organischen Chemie”, George Thieme Verlag, Stuttgart,
2nd ed., 1984, p. 176.
I‘
‘’