o-benzenedisulfonimide as reusable bronsted acid catalyst for acid-catalyzed organic reactions

Article abstract of DOI:10.1055/s-2008-1072564

Acid-catalyzed organic reactions, such as etherification, esterification, acetal synthesis, cleavage, and interconversion, and pinacol rearrangement were carried out in the presence of catalytic amounts of o-benzenedisulfonimide as Bronsted acid catalyst; the conditions were mild and selective. The catalyst was easily recovered and purified, ready to be used in further reactions, with economic and ecological advantages. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072564

PAPER
1379
o-Benzenedisulfonimide as Reusable Brønsted Acid Catalyst for
Acid-Catalyzed Organic Reactions
o
-Benzenedisulfonimid
a
e
as
R
eusa
r
ble
B
røn
g
ste
d
A
cid Ca
h
talyst erita Barbero,* Silvano Cadamuro, Stefano Dughera, Paolo Venturello
Dipartimento di Chimica Generale e Chimica Organica, Università, Via P. Giuria 7, 10125 Torino, Italy
Fax +39(11)6707642; E-mail: margherita.barbero@unito.it
Received 10 January 2008; revised 17 January 2008
be prepared starting from the commercially available di-
potassium o-benzenedisulfonate,3,6 anthranilic acid,7 o-
aminobenzenesulfonic acid,2–5,8 and o-bis(methylsulfa-
nyl)benzene.9 Currently, both o-benzenedisulfonyl chlo-
Abstract: Acid-catalyzed organic reactions, such as etherification,
esterification, acetal synthesis, cleavage, and interconversion, and
pinacol rearrangement were carried out in the presence of catalytic
amounts of o-benzenedisulfonimide as Brønsted acid catalyst; the
conditions were mild and selective. The catalyst was easily recov- ride and, very recently, o-benzenedisulfonimide are
ered and purified, ready to be used in further reactions, with eco-
commercially available. The high acidity of Brønsted acid
1 is known (pKa –4.1 at 20 °C),10 but, to the best of our
nomic and ecological advantages.
Key words: acid catalysis, ether synthesis, ester synthesis, acetal
synthesis, pinacol rearrangement
knowledge, it was shown for the first time to promote de-
hydrative reactions on various substrates.1a
There are many examples of acid-catalyzed reactions for
the straightforward dehydrative syntheses of ethers, es-
ters, and acetals from alcohols and suitable reactants, and
they are regularly revised in many handbooks dealing
with protective group chemistry. The functional groups
introduced and the simplicity of the methods, both of syn-
thesis and of cleavage, are extremely significant in organ-
ic chemistry.
Recently, we reported some preliminary encouraging re-
sults concerning the use of o-benzenedisulfonimide (1;
Figure 1) in catalytic amounts as Brønsted acid in some
acid-catalyzed organic reactions.1a Etherification, esterifi-
cation and acetalization of selected examples were exam-
ined in view of the synthetic significance and simplicity of
the dehydrative acid-catalyzed methods for their synthe-
sis.
The ether function is one of the most commonly used pro-
tective groups for the hydroxyl functionality, and many
methods are available for its formation and removal under
a wide variety of conditions.11 Apart from the Williamson
protocol, acid-catalyzed dehydration of alcohols repre-
sents the more direct synthesis of ethers, and has practical
and economic advantages; protic acids, Lewis acids, met-
al catalysts,12a–d solid resins,12e–h supercritical fluids,12i
ionic liquids,12j,k and surfactant-type catalysts12l have been
reported as catalysts or solvents for dehydrative etherifi-
cation and the interest for this reaction is still high today.
In this paper we wish to report on a more comprehensive
study on the advantages of sulfonimide 1 as a nontoxic,
nonvolatile, and noncorrosive recyclable acid catalyst in
such synthetic procedures. A further valuable aspect is the
easy recovery of 1 in high yield from the reaction mixture,
due to its complete solubility in water, and its reuse with-
out loss of catalytic activity in further and various reac-
tions, with economic and ecological advantages. All the
reactions considered here were conducted in open-air
flasks, analytical grade solvents were used, and the only
side product was water.
The success of literature methods of ether synthesis cata-
lyzed by Brønsted acids via alcohol dehydration is very
often dependent on the choice of the reactants (to avoid
isomerization and elimination reactions) and of the protic
acid catalyst; normally high acid concentrations and reac-
tion temperatures are required.11b,c Metal catalysts, the use
of which allows milder reaction conditions, are usually
expensive;12a–d solid acid resins, although selective and re-
cyclable, normally require high temperatures.12e–g Com-
pared to these methods, our procedures are characterized
by mild reaction conditions, short reaction times, and
good selectivity.
O2
S
NH
S
O2
1
Figure 1
o-Benzenedisulfonimide was described for the first time
in 1921 and 1926 by Holleman2 and Hurtley and Smiles,3
respectively; more recently, Hendrickson,4 Blaschette,5
and Davis6 and their co-workers reported modified proce- The starting point of our research in this field was the re-
dures of synthesis. The key intermediate for its prepara- covery of ether derivatives in Heck-type arylation reac-
tion is, however, o-benzenedisulfonyl chloride, which can tions of allylic alcohols in ethanol; such side products
were obtained from the in situ arylated allylic alcohols, by
dehydrative condensation with the solvent catalyzed by o-
benzenedisulfonimide.1b First, we studied the etherifica-
tion of the allylic alcohols 1,3-diphenylprop-2-en-1-ol
SYNTHESIS 2008, No. 9, pp 1379–1388
Advanced online publication: 27.03.2008
DOI: 10.1055/s-2008-1072564; Art ID: Z01308SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
8

1380
M. Barbero et al.
PAPER
(2a), 1-phenylprop-2-en-1-ol (2b), and 3-phenylprop-2-
en-1-ol (2c) with the primary and secondary aliphatic al-
cohols 3a–e (Scheme 1). Next, we applied the reaction to
non-phenyl-substituted allylic alcohols, namely cyclohex-
2-en-1-ol (2d) and 3-methylbut-2-en-1-ol (2e). All of our
results are reported in Table 1.
R3
OH
R2
R3
OR4
R2
1 (cat.)
R4OH
+
R1
(solvent)
R1
4a–o
2a–e
3a–e
2
R1 R2 R3
3
R4
a
b
c
d
e
Ph Ph
H
Ph
-(CH2)3-
Me
H
H
H
a
b
c
d
e
Et
During the course of the reactions we observed the exclu-
sive formation of the mixed ethers 4a–o only; these were
isolated by flash chromatography of the crude residue and
fully characterized. The reaction conditions seem to be
very selective for the allylic systems studied.
Ph
H
i-Pr
Bn
Bu
H
Me
H
n-C8H17
Scheme 1 o-Benzenedisulfonimide-catalyzed etherification
The reactions were carried out according to three different
procedures: (a) in solution of the aliphatic alcohols 3a–d 7, 14); (c) under solvent-free conditions (Method C;
(Method A; Table 1, entries 1, 2, 5, 6, 8, 9, 11); (b) in tet- Table 1, entries 10, 12, 13, 15, 16). In methods B and C,
rahydrofuran as solvent (Method B; Table 1, entries 3, 4, the aliphatic alcohols 3 were used in stoichiometric
Table 1 o-Benzenedisulfonimide-Catalyzed Etherification of Allylic Alcohols 2a–e with Aliphatic Alcohols 3a–e
Entry Reactants
Ratio
Amount Methoda Temp
Time
(h)
Product 4
Yieldb
(%)
2
3
2/3
1 (mol%)
(°C)
r.t.
4
R1
Ph
Ph
Ph
Ph
R2
Ph
Ph
Ph
Ph
R3
H
H
H
H
R4
1
2
3
4
5
2a
2a
2a
2a
2b
3a
3b
3c
3d
3a
5
5
5
5
5
A
A
B
B
A
2
4a
4b
4c
4d
Et
77 (81)
74 (77)
85 (90)
70
r.t.
0.25
1
i-Pr
Bn
Bu
1:1
1:2
r.t.
reflux
60
2.5
15
4e
4f
H
Ph
Ph
H
H
H
Et
Et
56
(4e/4f 1:1)c
6
7
2b
2b
3b
3d
5
5
A
B
60
15
55
4g
4h
H
Ph
Ph
H
H
H
i-Pr
i-Pr
40
(4g/4h 1:2)c
1:2
reflux
4i
4j
H
Ph
Ph
H
H
H
Bu
Bu
50
(4i/4j 1:2)c
8
9
2b
2b
2b
2c
2c
2d
2d
2e
3b
3b
3c
3b
3c
3c
3d
3e
20
20d
5
A
A
C
A
C
C
B
C
reflux
reflux
60
8
4h
4h
4k
4h
4k
4l
Ph
H
H
H
H
H
H
H
H
H
H
H
H
i-Pr
i-Pr
Bn
88
8
Ph
79
10
11
12
13
14
15
1:1.2
3
Ph
60 (60)
41
20
10
5
60
7e
4e
1.5
9
Ph
i-Pr
Bn
1:1
60
Ph
50
1:1.2
1:1.2
1:1.2
60
(CH2)3
(CH2)3
Bn
75f
31f
5
reflux
60
4m
Bu
5
6
4n
4o
Me
H
H
Me
H
n-C8H17
n-C8H17
28c
(4n/4o 1:1)
g
16
2e
3e
2:1
5
C
60
3.5
4n
4o
Me
H
H
Me
H
n-C8H17
n-C8H17
40c
(4n/4o
1:1.3)
g
a The reaction was carried out in the presence of an excess of alcohol 3 as solvent (Method A), in THF as solvent (Method B), and in the absence
of solvent (Method C).
b Yields refer to pure isolated products; yields in parentheses are of isolated products from reactions carried out in the presence of 10 mol% 1.
c Product ratio determined by GC analysis. The two isomers were isolated as pure products and partial mixture; spectroscopic data were obtained
from pure products.
d Instead of 1, 96% H2SO4 (20 mol%) was used as catalyst.
e By this time, reactant 2c was no longer present.
f Bis(cyclohex-2-enyl) ether (4p) was detected in trace amounts (entry 13) or isolated (18%; entry 14).
g Ether 4o bears two methyl groups in this position.
Synthesis 2008, No. 9, 1379–1388 © Thieme Stuttgart · New York

PAPER
o-Benzenedisulfonimide as Reusable Brønsted Acid Catalyst
1381
amounts or in slight excess relative to allylic alcohols 2.
All the methods were found to be suitable, and the choice
depends on the nature of the reacting alcohols.
OR4
H
OR4
H
H
OH
H
1 (cat.)
+ R4OH
+
H
Ph
Ph
Ph
H
2b
3a–d
4e,g,i
4f,h,j,k
The preferred catalytic amount of o-benzenedisulfon-
imide (1) was 5 mol% (Table 1); in some cases, it was in-
creased to 10 mol% to optimize the product yield (yield
values in parentheses in Table 1, entries 1–3, 10). In all
cases, o-benzenedisulfonimide (1) was recovered as a re-
cyclable catalyst in high yield after workup of the reaction
mixture. The reaction temperature was raised from room
temperature (Table 1, entries 1–3) to 60 °C (entries 5, 6,
10–13, 15, 16) or reflux (entries 4, 7–9, 14), when the
times required for conversion were too long at lower tem-
peratures.
R4
3
4
a
b
d
c
e, f
g, h
i, j
k
Et
i-Pr
Bu
Bn
Scheme 2
In the etherification of 3-phenylprop-2-en-1-ol (2c) with
3b and 3c, (E)-1-phenyl-3-isopropoxyprop-1-ene (4h)
and (E)-1-phenyl-3-benzyloxyprop-1-ene (4k) were iso-
lated, respectively, as pure products in modest yields
(Table 1, entries 11 and 12).
The etherification of 1,3-diphenylprop-2-en-1-ol (2a)
proceeded under very mild conditions (r.t., or reflux in
THF; Table 1, entries 1–4); the yields of the pure isolated
ethers 4a–d were good, and no traces of the symmetrical
ethers were detected. High reactivity and selectivity can
be explained by means of the resonance stabilization of
the allylic and benzylic intermediate carbocation. We nev-
er detected or isolated traces of dialkyl ethers from the re-
action mixtures; in fact, the reaction failed when it was
applied to octan-1-ol to obtain the dioctyl ether by either
Method B or C, at 90 °C, for prolonged reaction times, in
the presence of 10 mol% 1 as catalyst. Furthermore, we
carried out the reaction of 1,3-diphenylprop-2-en-1-ol
(2a) with 3c (2a/3c, 1:1; Method B) in the presence of an
equimolar amount of 1,3-diphenylpropan-1-ol; after the
workup, we isolated pure ether 4c in 90% yield and the
unchanged 1,3-diphenylpropan-1-ol in quantitative yield
(see experimental section).
The decreasing reactivity from 2a to 2c can be explained
in terms of lower stabilization by resonance of the car-
bocation intermediate.
Finally, we applied these reaction conditions to non-
phenyl-substituted allylic alcohols 2d and 2e (Table 1, en-
tries 13–16); the results were not as good, but could be op-
timized. Cyclohex-2-en-1-ol (2d) was reacted with benzyl
alcohol (3c) and butan-1-ol (3d) in the presence of 5
mol% of catalyst 1, by Method C or B, respectively; this
afforded pure ethers 4l (75% yield; Table 1, entry 13) and
4m (31% yield; entry 14). The symmetric bis(cyclohex-2-
en-1-yl) ether formed as byproduct 4p in the reaction mix-
ture; it was also isolated in 18% yield (Table 1, entry 14).
As expected, the etherification of 3-methylbut-2-en-1-ol
(2e) with octan-1-ol (3e) furnished, along with prenyl oc-
tyl ether (4n), the rearranged ether 3-methyl-3-(octyl-
oxy)but-1-ene (4o) by allylic rearrangement of the
intermediate carbocation; the low yield could be im-
proved only slightly by addition of an excess of the allylic
alcohol (Method C; Table 1, entries 15 and 16).
Lower reactivity was observed with allylic alcohols 2b
and 2c (Table 1, entries 5–12): heating and prolonged re-
action times were required (entries 5–10) and 2c did not
always undergo complete conversion into the desired
products (entries 11 and 12). In the dehydrative etherifica-
tion of 1-phenylprop-2-en-1-ol (2b), two isomers formed:
beside the expected ethers 4e, 4g, and 4i, compounds 4f,
4h, and 4j were recovered, respectively (Table 1, entries
5–7; Methods A and B; Scheme 2). They derived by the
well-known allylic rearrangement of the intermediate car-
bocation;13 the reaction is an equilibrium, but in the reac-
tion of 2b with 3b, we were able to optimize the reaction
conditions, by addition of 20 mol% acid catalyst 1, so that
only the more stable primary ether 4h was obtained in
good yield (Table 1, entry 8).
Next, ester synthesis was examined. The dehydrative di-
rect esterification of carboxylic acids 5a–c with alcohols
3c–e catalyzed by o-benzenedisulfonimide (1)
(Scheme 3) was carried out in view of the synthetic rele-
vance of the reaction both on laboratory and industrial
scale.14a,b,g Silica-gel supported sodium hydrogen sul-
fate,14c acidic ionic liquids,12j surfactant-type Brønsted ac-
ids,12l,14d acidic solid resins,14e,f or Lewis acids14h have
been used in recent applications of the reaction. Since it is
an equilibrium process, the reaction is usually performed
in the presence of a large excess of one of the reactants or
with continuous removal of the water formed as byprod-
uct; in our procedure both disadvantages were avoided.
Moreover, E-isomers were the only pure isolated prod-
ucts. To verify a possible role of the o-benzenedisulfon-
imide on such stereoselectivity, we repeated the reaction,
using sulfuric acid as catalyst; the same reaction condi-
tions gave the same result, but in lower yield (Table 1, en-
try 9, cf. entry 8).
We examined only a few examples (Scheme 3): the re-
agents were used in almost stoichiometric amounts, at
90 °C in toluene. Of the recyclable catalyst 1, 20–30
mol% was used, in the absence of dehydrating agents;
pure products were isolated by flash chromatography of
the crude residue after basic washing of the reaction mix-
ture to recover unchanged acids.
From the reaction of 2b with 3c, only rearranged ether 4k
was obtained (Table 1, entry 10; Method C).
Synthesis 2008, No. 9, 1379–1388 © Thieme Stuttgart · New York

1382
M. Barbero et al.
PAPER
and heterogeneous catalysis.15d Excess of alcohol, remov-
al of water, use of toxic or corrosive acids, high catalyst
amounts, and formation of side products can be draw-
backs of the reaction.
O
O
1 (cat.)
R4OH
+
R5
OH
R5
OR4
6a–d
toluene, 90 °C
3c–e
5a–c
R5
5
3
R4
Our method presents the advantages of mild reaction con-
ditions (at room temperature and in air) and short times;
good conversions to dimethyl acetals were obtained for
the aromatic 4-chlorobenzaldehyde (7a; Table 3, entry 1),
the conjugated cinnamic aldehyde (7b; entry 2) the acid-
sensitive thiophene-2-carbaldehyde (7c; entry 3), and 4-
tert-butylcyclohexan-1-one (7d; entry 4) by reaction with
methanol (3f). As expected, 4-acetylbenzaldehyde (7e) af-
forded the aldehyde dimethyl acetal 8e in 77% yield
(Table 3, entry 5).
a
b
c
Bn
PhCH=CH
2-MeC6H4
c
d
e
Bn
Bu
n-C8H17
Scheme 3 o-Benzenedisulfonimide-catalyzed esterification
The results are listed in Table 2: they clearly show de-
creasing reactivity and product yields from the nonconju-
gated phenylacetic acid (5a; Table 2, entries 1 and 2) to
the conjugated cinnamic acid (5b; entries 3 and 4; pro-
longed reaction times) and further on to the aromatic 2-
methylbenzoic acid (5c; entry 6; no reaction was ob-
served). Moreover, selective esterification of phenylacetic
acid (5a) over cinnamic acid (5b) with butan-1-ol (3d)
was achieved (Table 2, entry 5): acids 5a and 5b were
used in equimolar amounts to react with 3d (in slight ex-
cess) until GC analysis of the reaction mixture showed no
further change; esters 6a and 6d were isolated in 89% and
9% yield, respectively, along with the unchanged starting
acids 5a (9%) and 5b (88%), respectively. From all the re-
actions, o-benzenedisulfonimide (1) was recovered in
high yield and reused as catalyst for other reactions.
O
OMe
MeOH (3f), 1 (cat.)
R6
R6
OMe
1 (cat.)
7
8
HOCH
1
(cat.)
CH
OH (
9
)
O
R6
O
10
To further explore the synthetic usefulness of o-benzene-
disulfonimide (1), we carried out some acetalization,
Scheme
cleavage, and interconversion
4
o-Benzenedisulfonimide-catalyzed acetal synthesis,
transacetalization,
and
acetal-cleavage reactions
(Scheme 4, Table 3).
The optimal amount of catalyst 1 was 0.5–1 mol%
Acetalization of the carbonyl function of aldehydes or ke- (Table 3). Neutralization at the end of the reaction was
tones by reaction with an alcohol is amongst the most use- achieved by the addition of solid sodium bicarbonate. The
ful protective methods,15a–c and the development of new yields reported in Table 3 refer to pure products, isolated
procedures (reaction conditions or alcohol equivalents) is by flash column chromatography on silica gel deactivated
the subject of continuous efforts.12i,15d,e Dimethyl acetals, by triethylamine. The acetal formation was also effected
widely used protecting groups, have been prepared from with success in solvent: from the reaction between alde-
methanol by well-established methods of homogeneous hyde 7a and ethane-1,2-diol (9) (7a/9 1:3) in toluene at
Table 2 o-Benzenedisulfonimide-Catalyzed Esterification Reactionsa
Entry
Reactants
Ratio
Amount 1 Time
Product 6
Yieldb
(%)
5
3
5/3
(mol%)
25
(h)
1.5
1.5
10
6
R4
R5
1
2
3
4
5
5a
3d
3e
3c
3d
3d
1:1.1
1:1
6a
6b
6c
6d
Bu
Bn
90
5a
20
n-C8H17
Bn
Bn
85
5b
1:1
30
CH=CHPh
CH=CHPh
40c
37c
5b
1:1.1
1:1:1.1d
20
10
4
Bu
5a, 5b
20
6a
6d
Bu
Bu
Bn
CH=CHPh
89e
9e
6
5c
3d
1:1
20
3
6e
Bu
2-Tol
no reaction
a Reagents and conditions: 2, 3, 1, toluene, 90 °C, time (until completion or no further progress by GC analysis).
b Yields refer to pure isolated products.
c Unchanged acid 5b (53%, entry 3; 62%, entry 4) was recovered from the reaction mixtures.
d Ratio 5a/5b/3d.
e Esters 6a and 6d were isolated partially in mixture; yields were calculated on the basis of their GC ratio and 1H NMR spectra. Unchanged acids
5a (9%) and 5b (88%) were also recovered (quantities calculated by their ratio in 1H NMR spectra).
Synthesis 2008, No. 9, 1379–1388 © Thieme Stuttgart · New York

PAPER
o-Benzenedisulfonimide as Reusable Brønsted Acid Catalyst
1383
Table 3 o-Benzenedisulfonimide-Catalyzed Acetalization, Acetal Cleavage and Transacetalization
Entry Reactants
Ratio Amount
Solvent
Temp Time Products
Yielda,b
7, 8, or 10
3f or 9 7/9
1 (mol%)
0.5
(°C)
r.t.
(min) 7, 8, or 10
(%)
1
2
7a 4-ClC6H4CHO
3f
3f
–
–
MeOH
MeOH
10
10
8a 4-ClC6H4CH(OMe)2
85 (90)c
64 (72)c,d
7b PhCH=CHCHO
0.5
r.t.
8b PhCH=CHCH(OMe)2
3
7c
3f
–
0.5
MeOH
r.t.
10
8c
64 (65)c,d
CHO
S
CH(OMe)2
S
OMe
4
5
7d
3f
3f
–
–
0.5
0.5
MeOH
MeOH
r.t.
r.t.
10
20
8d
78
77
t-Bu
t-Bu
O
OMe
7e 4-AcC6H4CHO
8e 4-AcC6H4CH(OMe)2
O
6
7
7a 4-ClC6H4CHO
9
1:3
–
1
toluene
90
60
5
10a
87d
78
O
Cl
MeOH–H2O
(9:1)
8f
0.5
r.t.
7f
CH(OMe)2
CHO
8
9
8g
–
5
H2O
70
70
5
7g
70
CH(OMe)2
CHO
O
CH(OMe)2
10b
3f
9
–
5
5
MeOH
THF
reflux
8h
80
89
O
O
O
CH(OMe)2
10 8h
1:2
reflux 30
10b
a Yields refer to pure isolated products.
b Products were characterized by GC-MS and 1H NMR spectroscopy, and by comparison with authentic commercial samples.
c Yields in parentheses are of 8 obtained in the presence of 1 (1 mol%).
d Unchanged carbonyl compound 7 was recovered (entry 2: 7b, 23%; entry 3: 7c, 5%; entry 6: 7a, 11%).
90 °C for 60 min, dioxolane derivative 10a was isolated in
O
87% yield (Table 3, entry 6). o-Benzenedisulfonimide (1)
also successfully catalyzed some explorative reactions of
deprotection of acetals to aldehydes in alcohol–water or
water (Table 3, entries 7 and 8, respectively; pure alde-
hydes 7f and 7g were isolated in good yields) and trans-
acetalization in the reacting alcohol or in an inert solvent
(Table 3, entries 9 and 10, respectively; pure dimethyl
acetal 8h and cyclic acetal 10b were isolated in high
yield).
Ph3C CPh
a
12, 100%
Ph2C(OH) C(OH)Ph2
b
11
O
O
+
Ph2C
CPh2
13, 91%
Ph3C CPh
12, 8%
Scheme 5 o-Benzenedisulfonimide-catalyzed pinacol rearrange-
ment. Reagents and conditions: (a) 1 (20 mol%), toluene, 110 °C, 7 h;
(b) 1 (10 mol%), toluene, 90 °C, 1 h.
Pinacol rearrangement in the presence of o-benzenedisul-
fonimide (1) was examined next (Scheme 5). The reaction
of vic-diols is catalyzed by strong mineral acids or solid
acid catalysts,12j,k and it has been shown that epoxides are
intermediates in the rearrangement of certain diols.16 In
confirmation of this, heating of 1,1,2,2-tetraphenylethane-
1,2-diol (11, benzopinacol) in toluene in the presence of
o-benzenedisulfonimide (1) gave benzopinacolone (12) as
the sole product (100% yield) or tetraphenyloxirane (13)
as the main product (91% yield) (Scheme 5), the outcome
depending on the reaction conditions with regard to tem-
perature and amount of acid catalyst.
advantages and disadvantages of solid acid catalysts, in
this work we demonstrated the synthetic usefulness of o-
benzenedisulfonimide (1) in some of the most common
acid-catalyzed reactions, as a nontoxic, nonvolatile, and
noncorrosive recyclable acid catalyst, highly soluble in
both organic solvents and water. We considered some
examples of acid-catalyzed dehydrative etherification,
esterification, acetalization, transacetalization, acetal
cleavage, and pinacol rearrangement. The results obtained
were good and showed differences in reactivity and selec-
tivity of various substrates.
In conclusion, considering the ubiquitous use of strong
Brønsted acids in organic synthesis and bearing in mind
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1384
M. Barbero et al.
PAPER
1H NMR (200 MHz, CDCl3): d = 1.33 (t, J = 7.0 Hz, 3 H), 3.60 (su-
perimposed q, J = 7.0 Hz, 2 H diastereotopic), 4.98 (d, J = 6.8 Hz,
1 H), 6.38 (dd, J = 16.0, 6.8 Hz, 1 H), 6.68 (d, J = 16.0 Hz, 1 H),
7.25–7.50 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 15.72, 64.33, 82.86, 126.93 (2 C),
127.17 (2 C), 127.94, 128.00, 128.84 (4 C), 131.00, 131.45, 136.97,
141.86.
All the reactions were conducted in open-air flasks; analytical grade
reagents and solvents were used, and reactions were monitored by
GC and GC–MS. GC–MS data were recorded with an HP 5989B
mass-selective detector connected to an HP 5890 GC cross-linked
methylsilicone capillary column. 1H and 13C NMR spectra were re-
corded on a Bruker Avance 200 spectrometer at 200 and 50 MHz,
respectively, of samples in CDCl3, with chemical shifts reported rel-
ative to CDCl3. Column chromatography and TLC were performed
on Merck silica gel 60 (70–230 mesh ASTM) and GF 254, respec-
tively. Flash chromatography was carried out on silica gel (particle
size 0.032–0.063 mm). Et3N (1%) was always used as a mobile-
phase additive to prevent deacetalization. PE (bp 40–60 °C) was
used. Details of the reactions and yields for the pure (GC, GC–MS,
MS (EI, 70 eV): m/z (%) = 238 (70) [M+], 105 (100).
(E)-3-Isopropoxy-1,3-diphenylprop-1-ene (4b)20
Chromatography: PE–Et2O, 6:4; colorless oil; yield: 0.37 g (74%).
1H NMR (200 MHz, CDCl3): d = 1.14 (d, J = 6.0 Hz, 3 H), 1.18 (d,
J = 6 Hz, 3 H), 3.68 (app quin, J = 6 Hz, 1 H), 4.99 (d, J = 6.8 Hz,
1 H), 6.25 (dd, J = 15.8, 6.8 Hz, 1 H), 6.53 (d, J = 15.8 Hz, 1 H),
7.15–7.37 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 22.49, 22.68, 68.92, 79.81, 126.80
(2 C), 127.11 (2 C), 127.71, 127.82, 128.69 (4 C), 131.00, 131.40,
136.93, 142.22.
1
TLC, H NMR) isolated products are listed in Tables 1– 3. The
structures and purity of all the products were confirmed by compar-
ison of their spectral data (MS and 1H NMR) with those reported in
the literature or with those of available commercial samples. Com-
mercially available reagents and solvents were purchased from
Aldrich and were used without purification or distillation before
use; Dowex 50X8 ion-exchange resin was purchased from Fluka.
1,3-Diphenylprop-2-en-1-ol (4a) and 1,3-diphenylpropan-1-ol were
prepared by reduction of the commercially available 1,3-diphenyl-
prop-2-en-1-one with LiAlH4 in THF, as described in the litera-
ture.17
MS (EI, 70 eV): m/z (%) = 252 (16) [M+], 105 (100).
(E)-3-(Benzyloxy)-1,3-diphenylprop-1-ene (4c)21
Chromatography: PE–Et2O, 6:4; colorless oil; yield: 0.51 g (85%).
1H NMR (200 MHz, CDCl3): d = 4.54 (s, 2 H), 4.98 (d, J = 7.0 Hz,
1 H), 6.30 (dd, J = 16.0, 7.0 Hz, 1 H), 6.59 (d, J = 16.0 Hz, 1 H),
7.17–7.43 (m, 15 H).
13C NMR (50 MHz, CDCl3): d = 70.43, 81.93, 126.95 (2 C), 127.33
(2 C), 127.88, 128.06 (4 C), 128.74 (2 C), 128.88 (4 C), 130.61,
131.87, 136.90, 138.76, 141.47.
Ethers 4a–p by Etherification Catalyzed by o-Benzenedisulfon-
imide (1); General Procedures
Method A (alcohols 3a–d as solvents): o-Benzenedisulfonimide
(1; 5 mol%; 0.022 g, 0.1 mmol) was added to a soln of 2 (2a, 2b, or
2c, 2.0 mmol) in alcohol 3 (3a or 3b, 10 mL); the mixture was
stirred at the temperature reported in Table 1. The reaction was
monitored by TLC, GC, and GC–MS until complete disappearance
of the starting material. The mixture was evaporated under reduced
pressure and the residue was poured into Et2O–H2O (40 mL, 1:1).
The aqueous layer was separated and the organic extract was
washed with H2O (20 mL), dried (Na2SO4), and evaporated under
reduced pressure. The crude residue was chromatographed on a
short column; this provided products 4a,b,e,f,g,h.
MS (EI, 70 eV): m/z (%) = 300 (1) [M+], 181 (100).
(E)-3-Butoxy-1,3-diphenylprop-1-ene (4d)22
Chromatography: PE–Et2O, 9:1; colorless oil; yield: 0.37 g (70%).
1H NMR (200 MHz, CDCl3): d = 0.87 (t, J = 7.2 Hz, 3 H), 1.27–
1.45 (m, 2 H), 1.56–1.65 (m, 2 H), 3.31–3.53 (m, 2 H), 4.85 (d,
J = 7.2 Hz, 1 H), 6.25 (dd, J = 15.8, 7.2 Hz, 1 H), 6.56 (d, J = 15.6
Hz, 1 H), 7.16–7.34 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 14.18, 19.67, 32.20, 68.70, 82.80,
126.79, 127.02, 127.45, 127.84, 128.68, 130.94, 131.27, 136.88,
141.81.
Method B (THF as solvent): o-Benzenedisulfonimide (1; 5 mol%;
0.022 g, 0.1 mmol) was added to a soln of 2 (2a or 2b, 2.0 mmol)
and 3 (3c, 2.0 mmol or 3d, 4.0 mmol) in THF (10 mL), and the mix-
ture was stirred at the temperature reported in Table 1. The reaction
was monitored by TLC, GC and GC–MS; the workup was as above;
this afforded pure (by GC, GC–MS, TLC, 1H NMR) products
4c,d,i.
MS (EI, 70 eV): m/z (%) = 266 (37) [M+], 105 (100).
(E)-3-Ethoxy-3-phenylprop-1-ene (4e)23
Chromatography: PE–Et2O, 7:3; colorless oil; isolated partially in
mixture with (E)-3-ethoxy-1-phenylprop-1-ene (4f); total yield:
0.18 g (56%; 4e/4f, 1:1, by GC and 1H NMR).
1H NMR (200 MHz, CDCl3): d = 1.20 (t, J = 7.0 Hz, 3 H), 3.35–
3.53 (m, 2 H), 4.70 (d, J = 6.6 Hz, 1 H), 5.14 (d, J = 10.8 Hz, 1 H),
5.22 (d, J = 7.4, 7.2 Hz, 1 H), 5.92 (ddd, J = 17.0, 10.2, 6.8 Hz, 1
H), 7.22–7.32 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 15.53, 64.17, 83.11, 116.21,
127.01 (2 C), 127.75, 128.64 (2 C), 139.44, 141.56.
MS (EI, 70 eV): m/z (%) = 162 (60) [M+], 117 (100).
Method C (no solvent): o-Benzenedisulfonimide (1; 5 mol%;
0.055 g, 0.25 mmol) was added to a mixture of 2 (2b or 2c, 5.0
mmol) and BnOH (3c; 6.0 or 5.0 mmol for 2b or 2c, respectively),
and the mixture was stirred at 60 °C in an oil bath. The reaction was
monitored by GC and GC–MS; the workup was as above, and af-
forded pure product 4k.
Recovery of o-benzenedisulfonimide (1): The aqueous layer and
aqueous washings from the various reactions were collected and
evaporated under reduced pressure. The residue was passed through
a column of Dowex 50X8 ion-exchange resin (1.6 g resin/1 g prod-
uct); elution was with H2O. After removal of the H2O under reduced
1
pressure, virtually pure (by H NMR) 1 was recovered; mp 192–
194 °C (toluene) (Lit.18 192–194 °C).
(E)-3-Ethoxy-1-phenylprop-1-ene (4f)23,24
1H NMR (200 MHz, CDCl3): d = 1.19 (t, J = 7.0 Hz, 3 H), 3.49 (q,
J = 7.0 Hz, 2 H), 4.08 (d, J = 6.0 Hz, 2 H), 6.24 (dt, J = 15.8, 6.1 Hz,
1 H), 6.55 (d, J = 16.0 Hz, 1 H), 7.17–7.36 (m, 5 H).
Details of the reaction conditions and yields of products 4a–k are
listed in Table 1; chromatographic solvents and spectroscopic data
are reported below for each product.
13C NMR (50 MHz, CDCl3): d = 15.50, 65.90, 71.42, 126.52,
126.66 (2 C), 127.79, 128.72 (2 C), 132.40, 136.97.
MS (EI, 70 eV): m/z (%) = 162 (61) [M+], 105 (100).
(E)-1,3-Diphenyl-3-ethoxyprop-1-ene (4a)19
Chromatography: PE–Et2O, 6:4; colorless oil; yield: 0.37 g (77%).
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PAPER
o-Benzenedisulfonimide as Reusable Brønsted Acid Catalyst
1385
(E)-3-Isopropoxy-3-phenylprop-1-ene (4g)25
Chromatography: PE–Et2O, 7:3; colorless oil; isolated partially in
mixture with (E)-4h; total yield: 0.14 g (40%; 4g/4h, 1:2, by GC
and 1H NMR).
1H NMR (200 MHz, CDCl3): d = 1.09 (d, J = 6.2 Hz, 3 H), 1.14 (d,
J = 6.2 Hz, 3 H), 3.61 (app quin, J = 6.2 Hz, 1 H), 4.81 (d, J = 6.8
Hz, 1 H), 5.10 (d, J = 10 Hz, 1 H), 5.17 (d, J = 17.8 Hz, 1 H), 5.89
(ddd, J = 17.0, 10.2, 6.6 Hz, 1 H), 7.21–7.30 (m, 5 H).
3-Butoxycyclohex-1-ene (4m)30
Chromatography: PE–Et2O, 9.8:0.2; colorless oil; yield: 0.24 g
(31%).
1H NMR (200 MHz, CDCl3): d = 0.84 (t, J = 7.2 Hz, 3 H), 1.25–
1.80 (m, 8 H), 1.8–1.95 (m, 2 H), 3.34–3.49 (m, 2 H), 3.71–3.77 (m,
1 H), 5.70–5.80 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 14.13, 19.49, 19.62, 25.43, 28.53,
32.50, 68.20, 72.92, 128.28, 130.71.
MS (EI, 70 eV): m/z (%) = 154 (5) [M+], 81 (100).
13C NMR (50 MHz, CDCl3): d = 22.30, 22.65, 68.86, 80.14, 115.88,
127.03 (2 C), 127.61, 128.56 (2C), 139.92, 142.02.
MS (EI, 70 eV): m/z (%) = 176 (7) [M+], 117 (100).
Bis(cyclohex-2-en-1-yl) Ether (4p)31
Isolated as byproduct by flash chromatography of the crude mixture
of the reaction of Table 1, entry 14; NMR spectra are consistent
with a mixture of the two enantiomers and the mesoform.
(E)-1-Phenyl-3-isopropoxyprop-1-ene (4h)26
1H NMR (200 MHz, CDCl3): d = 1.16 (d, J = 6.0 Hz, 6 H), 3.64
(app quin, J = 6.2 Hz, 1 H), 4.09 (d, J = 6.0 Hz, 2 H), 6.26 (dt,
J = 15.8, 5.8 Hz, 1 H), 6.55 (d, J = 16.0 Hz,1 H), 7.17–7.36 (m, 5
H).
13C NMR (50 MHz, CDCl3): d = 22.35 (2 C), 68.93, 71.16, 126.66
(2 C), 127.06, 127.72, 128.70 (2 C), 131.96, 137.07.
Yield: 0.08 g (18%).
1H NMR (200 MHz, CDCl3): d = 1.36–2.09 (m, 12 H), 3.90–4.00
(m, 2 H), 5.60–5.79 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 19.44, 19.72, 25.40, 29.39, 29.84,
70.73, 70.78, 128.90, 129.04, 130.51, 130.58.
MS (EI, 70 eV): m/z (%) = 178 (5) [M+], 81 (100).
MS (EI, 70 eV): m/z (%) = 176 (28) [M+], 105 (100).
(E)-3-Butoxy-3-phenylprop-1-ene (4i)27
Chromatography: PE–Et2O, 9:1; colorless oil; isolated partially in
mixture with (E)-4j; total yield: 0.19 g (50%; 4i/4j, 1:2, by GC and
1H NMR).
1H NMR (200 MHz, CDCl3): d = 0.86 (t, J = 7.0 Hz, 3 H), 1.26–
1.44 (m, 2 H), 1.49–1.62 (m, 2 H), 3.27–3.45 (m, 2 H), 4.67 (d,
J = 6.6 Hz, 1 H), 5.13 (d, J = 11.0 Hz, 1 H), 5.20 (d, J = 18.4 Hz, 1
H), 5.90 (ddd, J = 17.0, 10.4, 6.6 Hz, 1 H), 7.20–7.30 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 14.16, 19.64, 32.16, 68.63, 83.17,
116.31, 126.98 (2 C), 127.68, 128.59 (2 C), 139.50, 141.65.
MS (EI, 70 eV): m/z (%) = 190 (23) [M+], 117 (100).
2-Methyl-4-(octyloxy)but-2-ene (4n)32
Chromatography: PE–Et2O, 9.8:0.2; colorless oil; isolated in mix-
ture with 4o (4n/4o, 40:60, by GC); total yield: 0.40 g (40%; 4n/4o,
1:1.3, by GC and 1H NMR).
1H NMR (200 MHz, CDCl3): d = 0.78–0.84 (m; 4n and 4o), 1.07–
1.30 (m; 4n and 4o), 1.36–1.55 (m; 4n and 4o), 1.61 and 1.68 (2 s,
6 H; 4n), 3.20 (t, J = 6.7 Hz, 2 H; 4o), 3.33 (t, J = 6.6 Hz, 2 H; 4n),
3.87 (d, J = 6.6 Hz, 2 H; 4n), 5.02 (d, J = 10.8 Hz, 1 H; 4o), 5.04 (d,
J = 18.4 Hz, 1 H; 4o), 5.20–5.32 (m, 1 H; 4n), 5.76 (dd, J = 17.6,
10.8 Hz, 1 H; 4o).
13C NMR (50 MHz, CDCl3): d = 14.30, 22.85, 26.05 (2 C), 26.41,
29.50, 29.69, 30.80, 32.03, 62.85, 67.41, 70.59, 74.94, 113.50,
121.60, 144.59.
(E)-3-Butoxy-1-phenylprop-1-ene (4j)28
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 7.2 Hz, 3 H), 1.26–
1.44 (m, 2 H), 1.49–1.63 (m, 2 H), 3.43 (t, J = 6.6 Hz, 2 H), 4.07 (d,
J = 5.8 Hz, 2 H), 6.24 (dt, J = 15.8, 6.0 Hz, 1 H), 6.55 (d, J = 15.8
Hz, 1 H), 7.15–7.36 (m, 5 H).
MS (EI, 70 eV): m/z (%) = 198 (10) [M+], 183 (20), 71 (100).
3-Methyl-3-(octyloxy)but-1-ene (4o)
Isolated as pure product and partially in mixture with 4n.
1H NMR (200 MHz, CDCl3): d = 0.78–0.84 (m, 3 H), 1.08–1.30 (m,
14 H), 1.36–1.56 (m, 4 H), 3.20 (t, J = 6.7 Hz, 2 H), 5.02 (d, J = 10.8
Hz, 1 H), 5.04 (d, J = 18.4 Hz, 1 H), 5.76 (dd, J = 17.6, 10.8 Hz, 1
H).
13C NMR (50 MHz, CDCl3): d = 14.29, 22.85, 26.05 (2 C), 26.41,
29.48, 29.69, 30.78, 32.04, 62.85, 74.94, 113.52, 144.58.
MS (EI, 70 eV): m/z (%) = 198 (10) [M+], 183 (48), 71 (100).
13C NMR (50 MHz, CDCl3): d = 14.17, 19.59, 32.09, 70.45, 71.62,
126.66 (3 C), 127.78, 128.73 (2 C), 132.28, 136.99.
MS (EI, 70 eV): m/z (%) = 190 (40) [M+], 105 (100).
(E)-3-(Benzyloxy)-1-phenylprop-1-ene (4k)29
Chromatography: PE–Et2O, 9:1; colorless oil; yield: 0.67 g (60%).
1H NMR (200 MHz, CDCl3): d = 4.17 (dd, J = 6.0, 1.4 Hz, 2 H),
4.55 (s, 2 H), 6.30 (dt, J = 16.0, 6.0 Hz, 1 H), 6.61 (d, J = 16.0 Hz,
1 H), 7.18–7.39 (m, 10 H).
Selective Etherification of 1,3-Diphenylprop-2-en-1-ol (2a) with
Benzyl Alcohol (3c) in the Presence of 1,3-Diphenylpropan-1-ol
According to the conditions of Method B, o-benzenedisulfonimide
(1; 5 mol%; 0.022 g, 0.1 mmol) was added to a soln of 2a (0.42 g,
2.0 mmol), 1,3-diphenylpropan-1-ol (0.43 g, 2.0 mmol), and BnOH
(3c; 0.22 g, 2.0 mmol) in THF (10 mL), and the mixture was stirred
at r.t. for 30 min. After the usual workup of the reaction mixture, the
crude residue was chromatographed on a short column (PE–Et2O,
6:4); this provided pure 4c (0.54 g, 90%) and unchanged 1,3-diphe-
nylpropan-1-ol (quantitative).
13C NMR (50 MHz, CDCl3): d = 70.99, 72.40, 126.30, 126.73,
127.90, 128.04, 128.66, 128.79, 132.75, 136.95, 138.50.
MS (EI, 70 eV): m/z (%) = 224 (1) [M+], 180 (59), 105 (100), 91
(89).
3-(Benzyloxy)cyclohex-1-ene (4l)29
Chromatography: PE–Et2O, 9.5:0.5; colorless oil; yield: 0.71 g
(75%).
1H NMR (200 MHz, CDCl3): d = 1.46–1.96 (m, 6 H), 3.88–3.92 (m,
1 H), 4.48 and 4.56 (2 d, J = 12 Hz, 2 H diastereotopic), 5.72–5.86
(m, 2 H), 7.20–7.30 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 19.49, 25.46, 28.58, 70.23, 72.39,
127.61, 127.84 (2 C), 128.00, 128.53 (2 C), 131.15, 139.29.
MS (EI, 70 eV): m/z (%) = 188 (10) [M+], 97 (45), 91 (100).
Esters 6a–d by Esterification Catalyzed by o-Benzenedisulfon-
imide (1); General Procedure
o-Benzenedisulfonimide (1; 25 mol%; 0.11 g, 0.5 mmol) was added
to a soln of 5 (5a or 5b, 2 mmol) and alcohol 3 (3c, 3d, or 3e; 2 or
2.2 mmol) in toluene (10 mL), and the mixture was stirred at 90 °C
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1386
M. Barbero et al.
PAPER
for 30 min. The mixture was evaporated under reduced pressure and
the residue was poured into Et2O–H2O (40 mL, 1:1). The aqueous
layer was separated and the organic extract was washed with H2O
(20 mL), dried (Na2SO4), and evaporated under reduced pressure.
The aqueous layer and aqueous washings were collected, evaporat-
ed under reduced pressure, and passed through a column of Dowex
50X8 ion-exchange resin to recover pure 1. The crude residue was
chromatographed on a short column (silica gel, PE–Et2O, 8:2); this
provided pure compounds 6. Details of the reactions and yields of
products 6a–e are listed in Table 2; spectroscopic data are reported
below for each product.
Selective Esterification of Phenylacetic Acid (5a) with Butan-1-
ol (3d) in the Presence of Cinnamic Acid (5b) (Table 2, entry 5)
o-Benzenedisulfonimide (1; 20 mol%; 0.09 g, 0.4 mmol) was added
to a soln of 5a (0.27 g, 2 mmol), 5b (0.30 g, 2 mmol), and 3d (0.16
g, 2.2 mmol) in toluene (10 mL), and the mixture was stirred at
90 °C for 4 h (GC analyses showed no more progress of the reac-
tion). The workup was as described above. Esters 6a and 6d were
obtained partially in mixture after purification by column chroma-
1
tography; yields were calculated from their GC ratio and H NMR
spectra. Unchanged acids 5a and 5b were recovered as described
above; yields were calculated from their ratio in 1H NMR spectra.
Butyl Phenylacetate (6a)33
Colorless oil; yield: 0.38 g (90%).
Acetal Synthesis, Cleavage, and Interconversion Catalyzed by
o-Benzenedisulfonimide (1); Typical Procedures
Thiophene-2-carbaldehyde Dimethyl Acetal (8c) (Table 3, entry
3)
1H NMR (200 MHz, CDCl3): d = 0.85 (t, J = 7.0 Hz, 3 H), 1.23–
1.34 (m, 2 H), 1.48–1.58 (m, 2 H), 3.56 (s, 2 H), 4.04 (t, J = 6.6 Hz,
2 H), 7.15–7.28 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 13.86, 19.27, 30.80, 41.66, 64.94,
127.21, 128.72 (2 C), 129.43 (2 C), 134.40, 171.88.
o-Benzenedisulfonimide (1; 0.5 mol%; 0.0022 g, 0.01 mmol) was
added to a soln of 7c (0.22 g, 2 mmol) in MeOH (3f; 5 mL), and the
mixture was stirred at r.t. for 10 min. The mixture was treated with
solid NaHCO3 and evaporated under reduced pressure and the resi-
due was poured into Et2O–H2O (40 mL, 1:1). The organic extract
was dried (Na2SO4) and evaporated under reduced pressure. The
crude residue was chromatographed on a short column (silica gel
deactivated by Et3N, PE–Et2O, 9.5:0.5); this provided pure (by GC,
GC–MS, TLC, 1H NMR) 8c.
Yield: 0.20 g (64%); colorless oil.36
1H NMR (200 MHz, CDCl3): d = 3.30 (s, 6 H), 5.58 (s, 1 H), 6.93–
6.97 (m, 1 H), 7.00–7.03 (m, 1 H), 7.24 (d, J = 5.0 Hz,1 H).
MS (EI, 70 eV): m/z (%) = 192 (5) [M+], 91 (100).
Octyl Phenylacetate (6b)33
Colorless oil; yield: 0.42 g (85%).
1H NMR (200 MHz, CDCl3): d = 0.80–0.86 (m, 3 H), 1.12–1.21 (m,
10 H), 1.52–1.60 (m, 2 H), 3.56 (s, 2 H), 4.03 (t, J = 7.0 Hz, 2 H),
7.14–7.24 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 14.29, 22.84, 26.03, 28.76, 29.36
(2 C), 31.96, 41.69, 65.23, 127.21, 128.72 (2 C), 129.44 (2 C),
134.42, 171.88.
13C NMR (50 MHz, CDCl3): d = 52.73 (2 C), 100.28, 125.63,
125.89, 126.87, 141.72.
MS (EI, 70 eV): m/z (%) = 158 (8) [M+], 127 (100).
MS (EI, 70 eV): m/z (%) = 248 (5) [M+], 91 (100).
Benzyl Cinnamate (6c)34
4-Chlorobenzaldehyde Ethylene Acetal (10a) (Table 3, entry 6)
o-Benzenedisulfonimide (1; 1 mol%; 0.0044 g, 0.02 mmol) was
added to a soln of 7a (0.28 g, 2 mmol) and 9 (0.37 g, 6 mmol) in
toluene (5 mL), and the mixture was stirred at 90 °C for 60 min. Af-
ter the usual workup, the crude residue was chromatographed on a
short column (PE–Et2O, 9.5:0.5).
Yield: 0.32 g (87%); colorless oil.37
1H NMR (200 MHz, CDCl3): d = 3.92–3.99 (m, 2 H), 4.02–4.09 (m,
2 H), 5.72 (s, 1 H), 7.29 (d, J = 8.8 Hz, 2 H), 7.36 (d, J = 8.8 Hz, 2
After completion of the reaction, unchanged cinnamic acid (5b) was
separated by washing of the organic extracts with 5% aq NaOH.
Usual workup of the organic phase and chromatographic purifica-
tion gave product 6c. The basic washings were acidified with 35%
HCl and then extracted with Et2O; after evaporation of the solvent,
pure acid 5b (by GC, GC–MS, 1H NMR) was recovered; yield: 0.14
g (53%).
Product 6c
Yield: 0.19 g (40%); white solid; mp 36–36.8 °C (PE) (Lit.31 38–
39 °C).
H).
13C NMR (50 MHz, CDCl3): d = 65.51 (2 C), 103.21, 128.10 (2 C),
128.75 (2 C), 135.20, 136.69.
MS (EI, 70 eV): m/z (%) = 184 (35) [M+], 183 (100).
1H NMR (200 MHz, CDCl3): d = 5.20 (s, 2 H), 6.44 (d, J = 16.0 Hz,
1 H), 7.31–7.34 (m, 8 H), 7.40–7.48 (m, 2 H), 7.68 (d, J = 16.0 Hz,
1 H).
13C NMR (50 MHz, CDCl3): d = 66.57, 118.08, 128.31 (2 C),
128.48 (4 C), 128.80, 129.10 (2 C), 130.55, 134.56, 136.26, 145.39,
167.00.
Citral (7f) (Table 3, entry 7)
o-Benzenedisulfonimide (1; 0.5 mol%; 0.0022 g, 0.01 mmol) was
added to a soln of 8f (0.40 g, 2 mmol) in MeOH–H2O (5 mL, 9:1),
and the mixture was stirred at r.t. for 5 min. After the usual workup,
the crude residue was chromatographed on a short column (PE–
Et2O, 9.5:0.5); this provided pure 7f, whose spectral data were iden-
tical to those of a commercially available sample.
MS (EI, 70 eV): m/z (%) = 238 (25) [M+], 131 (100).
Butyl Cinnamate (6d)35
Unchanged cinnamic acid 5b was recovered as described above.
Yield: 0.26 g (80%); colorless oil.
Product 6d
Colorless oil; yield: 0.15 g (37%).
1H NMR (200 MHz, CDCl3): d = 0.90 (t, J = 7.3 Hz, 3 H), 1.38 (app
sext, J = 7.3 Hz, 2 H), 1.63 (app quin, J = 6.9 Hz, 2 H), 4.15 (t,
J = 6.6 Hz, 2 H), 6.38 (d, J = 16.0 Hz, 1 H), 7.30–7.33 (m, 3 H),
7.44–7.49 (m, 2 H), 7.62 (d, J = 16.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 13.96, 19.40, 30.97, 64.63, 118.47,
128.24 (2 C), 129.06 (2 C), 130.40, 134.66, 144.75, 167.31.
MS (EI, 70 eV): m/z (%) = 204 (20) [M+], 131 (100).
Phenylacetaldehyde Dimethyl Acetal (8h) (Table 3, entry 9)
o-Benzenedisulfonimide (1; 5 mol%; 0.022 g, 0.1 mmol) was added
to a soln of 10b (0.33 g, 2 mmol) in MeOH (10 mL), and the mixture
was stirred at reflux for 5 min. After the usual workup, the crude
residue was chromatographed on a short column (PE–Et2O,
9.5:0.5); this provided pure 8h, whose spectral data were identical
to those of a commercially available sample.
Yield: 0.26 g (80%); colorless oil.
Synthesis 2008, No. 9, 1379–1388 © Thieme Stuttgart · New York

PAPER
o-Benzenedisulfonimide as Reusable Brønsted Acid Catalyst
1387
Phenylacetaldehyde Ethylene Acetal (10b) (Table 3, entry 10)
o-Benzenedisulfonimide (1; 5 mol%; 0.022 g, 0.1 mmol) was added
to a soln of 8h (0.33 g, 2 mmol) and 9 (0.12 g, 4 mmol) in THF (5
mL), and the mixture was stirred at reflux for 30 min. After the usu-
al workup, the crude residue was chromatographed on a short col-
umn (PE–Et2O, 9.5:0.5); this provided pure 10b, whose spectral
data were identical to those of a commercially available sample.
MS (EI, 70 eV): m/z (%) = 332 [M+ – 16], 243 (100).
Tetraphenyloxirane (13)42 by Pinacol Rearrangement
o-Benzenedisulfonimide (1; 10 mol%; 0.033 g, 0.15 mmol) was
added to a soln of 11 (0.55 g, 1.5 mmol) in toluene (10 mL), and the
mixture was stirred at 90 °C for 2 h. The reaction was monitored by
TLC, GC, and GC–MS analyses until complete disappearance of
11. After the usual workup, purification of the crude residue by
flash chromatography (PE–CH2Cl2, 8:2) yielded pure 13; yield:
0.46 g (91%); and rearranged product 12; yield: 0.04 g (8%).
Yield: 0.29 g (89%); colorless oil.
Details of the reactions and yields of products 7f,g, 8a–e,h, and
10a,b are listed in Table 3. Chromatography for all the products:
PE–Et2O, 9.5:0.5. The structures and purity of the products 7f,g,
8a,h, and 10a,b were confirmed by comparison of their spectral
data (MS and 1H NMR) with those of commercially available sam-
ples of analytical purity (Aldrich).
Product 13
Colorless needles; mp 211.1–212.0 °C (toluene–PE) (Lit.38 211–
213 °C).
1H NMR (200 MHz, CDCl3): d = 7.03–7.09 (m, 10 H), 7.11–7.20
(m, 8 H).
13C NMR (50 MHz, CDCl3): d = 74.03 (2 C), 127.26 (4 C), 127.76
(8 C), 128.42 (8 C), 138.79 (4 C).
Cinnamaldehyde Dimethyl Acetal (8b)15d,38
Colorless oil; yield: 0.23 g (64%).
1H NMR (200 MHz, CDCl3): d = 3.32 (s, 6 H), 4.91 (d, J = 4.2 Hz,
1 H), 6.10 (dd, J = 16.2, 4.8 Hz, 1 H), 6.67 (d, J = 16.2 Hz, 1 H),
7.20–7.37 (m, 5 H).
MS (EI, 70 eV): m/z (%) = 348 (40) [M+], 165 (100).
13C NMR (50 MHz, CDCl3): d = 52.93 (2 C), 103.11, 125.90,
126.94 (2 C), 127.80 (2 C), 128.32, 133.79, 136.29.
Acknowledgment
This work was supported by the Italian MIUR and by the Università
degli Studi di Torino.
MS (EI, 70 eV): m/z (%) = 178 (30) [M+], 147 (100).
4-tert-Butylcyclohexanone Dimethyl Acetal (8d)15d,36
Colorless needles; yield: 0.31 g (78%); mp 38–39 °C (pentane)
(Lit.39 38 °C).
References
1H NMR (200 MHz, CDCl3): d = 0.78 (s, 9 H), 0.90–1.25 (m, 5 H),
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4-Acetylbenzaldehyde Dimethyl Acetal (8e)36
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IR (CCl4): 1691 (CO) cm–1.
1H NMR (200 MHz, CDCl3): d = 2.52 (s, 3 H), 3.24 (s, 6 H), 5.36
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mixture was stirred at 110 °C for 7 h. The reaction was monitored
by TLC, GC, and GC–MS analyses until complete conversion into
the desired product. The mixture was poured into Et2O–H2O (40
mL, 1:1), the aqueous layer was separated, and the organic extract
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der reduced pressure. The crude residue was purified by flash chro-
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1H NMR (200 MHz, CDCl3): d = 7.09–7.24 (m, 18 H), 7.59–7.63
(m, 2 H).
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127.99 (6 C), 131.10 (6 C), 131.25 (2 C), 131.88, 137.66, 143.39 (3
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IR (CCl4): 1684 (CO) cm–1.
Synthesis 2008, No. 9, 1379–1388 © Thieme Stuttgart · New York

1388
M. Barbero et al.
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