o-Benzenedisulfonimide as a reusable Bronsted acid catalyst for Ritter-type reactions

Article abstract of DOI:10.1002/ejoc.200800931

Reactions between various benzyl alcohols or tert-butyl alcohol and nitriles were carried out in the presence of catalytic amounts (usually 10-20 mol-%) of o-benzenedisulfonimide as a Bronsted acid catalyst; the reaction conditions were mild and the yields of amides were good. The catalyst was easily recovered and purified, ready to be used in further reactions, with economic and ecological advantages. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Full text of DOI:10.1002/ejoc.200800931

FULL PAPER
DOI: 10.1002/ejoc.200800931
o-Benzenedisulfonimide as a Reusable Brønsted Acid Catalyst for Ritter-Type
Reactions
[a]
[a]
[a]
[a]
Margherita Barbero, Stefano Bazzi, Silvano Cadamuro, and Stefano Dughera*
Keywords: Homogeneous catalysis / Amides / Nitriles / Ritter reaction / Brønsted acid
Reactions between various benzyl alcohols or tert-butyl
was easily recovered and purified, ready to be used in further
alcohol and nitriles were carried out in the presence of cata- reactions, with economic and ecological advantages.
lytic amounts (usually 10–20 mol-%) of o-benzenedisulfon-
imide as a Brønsted acid catalyst; the reaction conditions
were mild and the yields of amides were good. The catalyst
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
[
7b–7e]
Lewis acids,[8]
Introduction
as a Brønsted acid or other protic acids,
[
9]
[10]
metal complexes, solid-supported acids,
and many
We have recently[1] reported the use of o-benzenedisul-
fonimide (1) in catalytic amounts as a Brønsted acid in
some acid-catalyzed organic reactions such as etherifi-
cation, esterification and acetalization under very mild and
selective conditions. The catalyst was easily recovered and
purified, ready to be used in further reactions, with eco-
nomic and ecological advantages.
[11]
others.
The main disadvantages of these methods are
often the use of toxic, corrosive, and expensive catalysts,
and their recovery and reuse is often impossible.
In this paper we wish to report a comprehensive study
of the reactions between various alcohols and nitriles in the
presence of catalytic amount of 1 to provide amides in
Ritter fashion.
o-Benzenedisulfonimide (1, Figure 1) has a high acidity
[
2]
(
pk –4.1 at 20 °C) and was described for the first time in
a
[
3]
1921 and 1926; however, modified procedures of its syn-
[
4]
Results and Discussion
thesis have been proposed more recently. The key interme-
diate for its preparation is o-benzenedisulfonyl chloride,
which is now commercially available. Very recently, o-
benzenedisulfonimide itself has also become commercially
available.
To begin with, we studied the reaction between di-
phenylmethanol (2a, Scheme 1) and MeCN (3a) in the pres-
ence of catalytic amounts of 1 (10 mol-%). The reaction was
carried out in the presence of an excess of 3a as solvent and
proceeded under mild conditions. N-(Diphenylmethyl)-
acetamide (4a) was obtained in high yield (89%; Table 1,
Entry 1). On monitoring of the progress of this reaction by
GC-MS, the formation of bis(diphenylmethyl) ether (5a)
was also observed; however, the quantity of 5a diminished
in the course of the reaction, and the compound had com-
pletely disappeared after 8 h. On the other hand, we were
able to isolate and characterize 5a on stopping the reaction
after 2 h.
Furthermore, 1 was recovered in excellent yield (86%),
simply on concentrating the aqueous layer and washings
under reduced pressure as reported in the Experimental
Section. The recovered 1 was reused as catalyst in other two
consecutive reactions between 2a and 3a. The results are
listed in Table 1: the reaction times increased in the course
of the different reactions, but the yields of 4a and the recov-
ery of 1 were always good.
Figure 1. o-Benzenedisulfonimide (1).
In 1948, Ritter and co-workers reported the efficient syn-
thesis of amides through the reactions between alkenes and
many nitriles in the presence of sulfuric acid.[5] Over the
years, mainly alcohols have also come to be used in place
[
6]
of alkenes, and several methodologies have very recently
been employed for Ritter reactions in which sulfuric acid is
[
7a]
replaced variously by 2,4-dinitrobenzenedisulfonic acid
[
a] Dipartimento di Chimica Generale
e Chimica Organica
dell’Università di Torino,
Corso M. d’Azeglio 48, 10125 Torino, Italy
Fax: +39-011-6707642
In light of the above, we think that the reaction proceeds
described in Scheme 2, in
which the interaction between 2a and 1 generates the prod-
E-mail: stefano.dughera@unito.it
[
7a]
through the catalytic cycle
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
430
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 430–436

Reusable Brønsted Acid Catalyst
(
Method A). Also worthy of note is the importance of these
[
7a]
compounds in biological and medical fields and their use
[
7a]
as protecting groups. The results, reported in Table 2, al-
low the following conclusions to be drawn. Either with ali-
phatic (3a, 3g) or aromatic (3b, 3d–f) substrates the result
obtained were good, independently of any electronic effects
of the groups on an aromatic ring (Table 2, Entries 1, 3, 6,
8, 10, 12). In contrast, steric effects were important: with
regard to 3c, the presence of a methyl group in the ortho
position drastically reduced the yield (Table 2, Entry 5).
Scheme 1. Reactions between 2a and 3a.
Table 1. Consecutive reactions with recycled 1.
Entry
Time [h]
Yield (%) of 4a[a]
Recovery (%) of 1
b]
[c]
1
2
3
8
15
24
89[
86, 0.19 g
[
d,e]
[f]
84[
89, 0.17 g
g,h]
84
100, 0.17 g
[
a] Yields refer to the pure products. [b] The reaction was per-
formed with 2a (10 mmol, 1.84 g) and 1 (10 mol-%, 0.22 g,
mmol). [c] The recovered 1 was reused in Entry 2. [d] The reaction
was performed with 2a (8.7 mmol, 1.60 g) and 1 (10 mol-%, 0.19 g,
.87 mmol). [e] 2a (0.10 g, 6%) was also recovered. [f] The reco-
vered 1 was reused in Entry 3. [g] The reaction was performed with
a (7.76 mmol, 1.43 g) and 1 (10 mol-%, 0.17 g, 0.77 mmol). [h] 2a
0.11 g, 8%) was also recovered.
1
0
2
(
uct 6a. This, reacting with 3a, gives rise to compound 7a,
which undergoes a nucleophilic attack by the water pro-
duced in the first step. In this manner, through the interme-
diate 8a, 4a is formed, with regeneration of 1, ready to start
another catalytic cycle. Note that 6a, reacting with 2a, fur-
nishes 5a, regenerating 6a.
Scheme 3. Reactions between alcohols 2 and nitriles 3.
Furthermore, with respect to compounds 2, electronics
effects were fundamental. In particular, on treatment of 2e
(
bearing two electron-donating groups) with 3a, no traces
of 4n were detected, but bis(4-methoxyphenyl)methane and
,4Ј-dimethoxybenzophenone were recovered (Table 2, En-
4
[
12]
try 26). It is known from the literature that diarylmethyl
isopropyl ethers, under catalytic acid conditions, undergo
disproportionation reactions with selective hydride transfer
to the more electrophilic bis-benzylic carbon centres and
with the formation of the corresponding diarylmethanes
Scheme 2. Catalytic cycle.
On these grounds, alcohols 2a–f were treated with nitriles and acetone. Under our conditions, ether 5n was able to
a–g, either aliphatics or aromatics (Scheme 3), in the react in the same way, most probably due to the presence
3
presence of catalytic amounts of 1 (10 mol-%) in order to of two methoxy groups. With 5b, bearing only one methoxy
synthesize amides 4a–o under easy and mild conditions group, however, no disproportionation reaction occurred
Eur. J. Org. Chem. 2009, 430–436
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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431

M. Barbero, S. Bazzi, S. Cadamuro, S. Dughera
FULL PAPER
Table 2. Synthesis of amides 4 from alcohols 2 and nitriles 3.
Entry Reactants Method Time [h] Temp. [°C] Yields (%)[a,b]
Table 2, Entries 2, 4, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25), in
which the nitriles 3 were used in stoichiometric amounts
relative to alcohols 2. The reactions were usually slower, but
the yields were always good, with evident economic and
ecological advantages.
[
c]
d]
e]
d]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2a, 3a
2a, 3a
2a, 3b
2a, 3b
2a, 3c
2a, 3d
2a, 3d
2a, 3e
2a, 3e
2a, 3f
2a, 3f
2a, 3g
2a, 3g
2b, 3a
2b, 3a
2b, 3b
2b, 3b
2c, 3a
2c, 3a
2c, 3b
2c, 3b
2d, 3a
2d, 3a
2d, 3b
2d, 3b
2e, 3a
2f, 3a
A
B
A
B
A
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
A
8
24
7
reflux
75
4a, 89
4a, 94
4b, 87
4b, 87
[
[
[
100
100
100
100
100
100
100
reflux
75
reflux
75
reflux
75
100
100
reflux
75
100
100
reflux
75
100
100
reflux
75
16
30
24
48
24
48
48
84
24
48
5
16
3
16
24
40
8
24
5
16
5
12
2
24
To explore the synthetic usefulness of o-benzenedisulfon-
imide (1) in Ritter-type reactions further, we also investi-
gated three other types of alcohols besides alcohols 2. We
first studied the reactions between 1-arylethanols 9a–e and
nitriles 3a and 3b (Scheme 4); the results are listed in
Table 3. It should be noted that traces of corresponding vi-
nylbenzenes were always detected by GC-MS; obviously,
their origin was due to the competitive elimination. Good
yields of amides 10 were usually obtained (Table 3, En-
tries 1–3, 5), but even in this case the electronic effects of
the substituents on the aromatic rings of 9 were very impor-
tant. In fact, on treatment of 9c (bearing a methoxy group
in the para position) with 3a, no traces of 10d were de-
tected. The only product was 1,3-bis(4-methoxyphenyl)but-
1-ene (Table 3, Entry 4). In contrast, when the methoxy
group was in the meta position (9b, Table 3, Entry 3), 10c
was isolated after a short reaction time.
[
f]
4c, 30
4d, 74
[
d]
[
d]
4d,76
4e, 80
4e, 74
4f, 73
[
d]
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
[
d]
4f, 75
4g, 99
4g, 81
4h, 85
4h, 80
4i, 77
[
d]
[
d]
[
d]
4i, 79
[
d, g]
4j, 97
[
d,h]
4j, 88
[
h]
4k, 80
4k, 77
[
d,h]
[
d]
d]
4l, 97
4l, 91
[
4m, 98
4m, 87
[
d]
[
i]
4n,–
[
j]
4o, 51
[
a] Yields refer to the pure products. [b] The presence of ethers 5
was always detected by GC-MS analysis in all the reactions with
the exception of Entry 26; compounds 5 disappeared during the
reactions. [c] The reaction was also performed with 1 (100 mol-%,
2
.19 g, 10 mmol). No traces of the possible N-diphenylmethyl-o-
benzenedisulfonimide were detected. [d] The crude residues were
amides 4 in a virtually pure state. No columns were necessary to
purify the products. [e] The crude residue was washed with pentane
(
10 mL) in a Buchner funnel to afford pure 4b. [f] Ether 5a {MS
+
+
(EI): m/z = 350 [M] } and 2a {MS (EI): m/z = 184 [M] } were both
detected in the GC-MS analyses of the crude residue. However, it
was not possible to obtain them pure. [g] The reaction was per-
formed with 1 (20 mol-%, 0.44 g, 2 mmol). With 1 (10 mol-%,
0
8
0
.22 g, 1 mol) the reaction time was 48 h and the yield of 4j was
8% (2.77 g). [h] The reaction was performed with 1 (20mol-%,
.44 g, 2 mmol). [i] No traces of amide 4n were detected. Bis(4- Scheme 4. Reactions between alcohols 9 and nitriles 3.
methoxyphenyl)methane (0.95 g, 42% yield), and 4,4Ј-dimeth-
oxybenzophenone (1.41 g, 58% yield) were isolated from a flash
column (eluent: petroleum ether/ethyl acetate, 9:1). [j] Bis(2,4,6-tri-
Probably there is a greater delocalization of the positive
charge of the carbocation when the methoxy group is situ-
ated in the para position, and for this reason the latter is
less available to nucleophilic attack by 3a.
+
methylphenyl)methane {MS (EI): m/z = 252 [M] } and bis(2,4,6-
+
trimethylphenyl)methanone {MS (EI): m/z = 266 [M] } were de-
tected in the GC-MS+ analyses of the crude residue. However, it
was not possible to obtain them pure.
On these grounds, the elimination reaction happens pref-
erentially, and the resulting 4-methoxystyrene, reacting with
1-(4-methoxyphenyl)ethyl cation, furnishes 1,3-bis(4-meth-
(Table 2, Entries 14, 16). In contrast, in the presence of elec- oxyphenyl)but-1-ene. On the other hand, when the methoxy
tron-withdrawing groups (Table 2, Entries 18, 20) the reac- group is situated in the meta position, because the positive
tions were considerably slower, but the yields of 4j and 4k charge of the carbocation is less delocalized, the latter is
were always good. Moreover, it seems that methyl groups easily attacked by 3a, with the formation of 10c. In the pres-
in the ortho positions (2f) caused a decrease in the yield of ence of electron-withdrawing groups (Table 3, Entry 6) the
4o (Table 2, Entry 27). However, the low amounts were due reaction was slowed down so much that only traces of 10f
to the same side-reaction (disproportionation) as described were detected.
before (Table 2, Entry 26). In fact, GC-MS analyses showed
Next, reactions between tert-butyl alcohol (11) and ni-
the presence of the corresponding diarylmethane and triles 3a–c, 3e and 3h were examined (Scheme 5) and the
ketone.
results are reported in Table 4. This reaction is useful to
It is interesting to remark that the reactions could also prepare bulky amides, which may be hydrolysed to provide
[
9a]
be carried out under solvent-free conditions (Method B; hindered amines.
432
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 430–436

Reusable Brønsted Acid Catalyst
Table 3. Synthesis of amides 10 from alcohols 9 and nitriles 3.
Table 4. Synthesis of amides 12 from alcohol 11 and nitriles 3.
Entry Reactants
Time [h]
Temp. [°C] Yields (%)[a,b]
Entry
Reactant
Temp. [°C]
Yields (%)[a,b]
10a, 93[
c,d]
1
2
3
4
5
3a
3b
3c
3e
3h
reflux
100
100
100
reflux
12a, 83[c]
1
2
3
4
5
6
9a, 3a
9a, 3b
9b, 3a
9c, 3a
9d, 3a
9e, 3a
48
8
15
0.5
27
96
reflux
100
reflux
reflux
reflux
reflux
[
e]
[d,e,f]
10b, 94[
12b, 80
f]
[g]
10c, 63
12c, traces
10d, –[
g]
12d, 77
12e, 56
[h]
10e, 72
10f, traces[
h]
[a] Yields refer to the pure products. [b] No traces of the possible
[
a] Yields refer to the pure products. [b] Traces of styrenes and the
di-tert-butyl ether were detected. [c] The reaction was performed
with 3a (10 mmol, 0.41 g) and an excess of 11 (5 mL) at reflux for
72 h. Compound 11 was evaporated under reduced pressure and
the crude residue was filtered on a short flash column, with elution
with petroleum ether/ethyl acetate (9:1) to provide pure amide 12a.
[d] When the reaction was performed with equimolar amounts of
reactants 3b and 11 (10 mmol, 1.03 g and 10 mmol, 0.74 g respec-
tively), only traces of 12b were detected by GC-MS after 48 h.
[e] The reactions was also performed with 3b (10 mmol, 0.41 g) and
an excess of 11 (5 mL) at reflux for 20 h. The usual workup fur-
nished 12b (1.26 g, 73% yields). [f] When the reaction was per-
formed with 1 (10 mol-%, 0.22 g, 1 mmol), only traces of 12b were
detected after 48 h by GC-MS. [g] Only traces of 12c {MS (EI): m/z
presence of bis(diarylethyl) ethers were always detected by GC-MS
in all the reactions with the exceptions of Entries 4 and 6; the ethers
disappeared during the reactions. [c] The reaction time was only
2
(
4 h and the yield of 10a was 83% (1.35 g) in the presence of 1
20 mol-%, 0.44 g, 2 mmol). [d] The reaction was also performed
with 1 (100 mol-%, 2.19 g, 10 mmol). No traces of the possible N-
1-phenylethyl)-o-benzenedisulfomide were detected. [e] After 48 h
(
at reflux, with 1 (20 mol-%, 0.44 g, 2 mmol) and equimolar
amounts of reactants 9a and 3b (10 mmol, 1.22 g and 10 mmol,
1
.03 g respectively) the reaction was not complete. [f] The reaction
was performed with 1 (20 mol-%, 0.44 g, 2 mmol). [g] No traces of
amide 10d were detected. 1,3-Bis(4-methoxyphenyl)but-1-ene
+
(
0.72 g, 53% yield) was isolated from a flash column (eluent: petro-
= 191 [M] } were detectable by GC-MS after 48 h. [h] Because 12d
leum ether/ethyl acetate, 9:1). [h] On GC-MS analyses, besides the
decomposed on the chromatography column, the reaction was per-
formed with an excess of 11 (5 mL), 3e (10 mmol, 0.41 g) and 1
(40 mol-%, 0.88 g, 4 mmol) at reflux for 72 h. The usual workup
furnished 12d (1.47 g, 77% yield) virtually pure. When the reaction
was performed with 1 (20mol-%, 0.44 g, 0.2 mol) the reaction time
was longer (168 h) and the yield of 12d was lower (1.05 g, 56%).
+
predominant 9e {MS (EI): m/z = 167 [M] }, only traces of amide
+
1
0f {MS (EI): m/z = 208 [M] } were detected, also in the presence
of 1 (20 mol-%, 0.44 g, 2 mmol).
disulfonimides. Moreover, in our previous paper[13] we de-
scribed the preparation of arenediazonium o-benezenedisul-
fonimides, by diazotization of aromatic amines with iso-
pentyl nitrite in the presence of 1.
Scheme 5. Reactions between alcohol 11 and nitriles 3.
The yields of amides 12 were usually satisfactory, with
the exception of the bulky 3c (Table 4, Entry 4), for which
steric effects became important. However, it must be
stressed that use of 20 mol-% amounts of catalyst 1 was
necessary for the completion of all the reactions.
Scheme 6. Reactions between alcohols 13 and compound 3a.
An X-ray analysis of one of these arenediazonium o-be-
Finally, we studied the behaviour of benzyl alcohols 13a–
d (Scheme 6), and the results, reported in Table 5, were nezenedisulfonimide confirmed its ionic nature. This arti-
[
13]
clearly less positive. First of all, with 10 or 20 mol-% cle also reports that the thermal decomposition of these
amount of catalyst 1 no traces of amide 14b were detected salts results in two products, one of which is the result of
(
Table 5, Entries 3, 4). It was necessary to increase the loss of nitrogen and aryl attack at the nitrogen atom of 1.
amount of 1 to 40 mol-% (Table 5, Entries 1, 5) or 100 mol- Possibly the formation of 15 occurs on heating of 13 with
(Table 5, Entries 1, 2, 5, 6) to obtain 14a or 14b in moder- stoichiometric amounts of 1, in spite of the poor nucleophi-
%
ate yields. However, it must be stressed that, despite the licity. Moreover, no traces of possible N-substituted o-
large amounts of 1 required, it was at least recovered in benzenedisulfonimides were detected when 2a or 9a were
excellent yield (80%). Moreover, besides 14a and 14b, N- allowed to react in the presence of a 100 mol-% quantity of
benzyl-o-benzenedisulfonimides 15a and 15b were also iso- 1. In this last case, it is possible that the greater steric hin-
lated (Table 5, Entries 3–6). The formation of the latter drance of 2 and 9 could prevent the formation of N-substi-
compounds was very surprising. The anion of 1 is a poor tuted o-benzenedisulfonimides. On treatment of 13c with 3a
[
4a]
[1]
nucleophile
and in our prior research we have never a not negligible amount of bis(4-methoxyphenyl)methane
detected the presence of possible N-substituted o-benzene- was also recovered (Table 5, Entry 7). The formation of this
Eur. J. Org. Chem. 2009, 430–436
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
433

M. Barbero, S. Bazzi, S. Cadamuro, S. Dughera
ica gel (particle size 0.032–0.063 mm). Et N (1%) was always used
FULL PAPER
Table 5. Synthesis of amides 14 from alcohols 13 and compound
3
3a.
as a mobile phase additive to prevent the hydrolysis of amides.
Petroleum ether (PE) refers to the fraction boiling in the 40–70 °C
range. H NMR and C NMR spectra were recorded with a
Bruker Avance 200 spectrometer at 200 and 50 MHz, respectively.
Entry Reactant Amount (%) of 1 Time [h] Yields (%)[a]
1
13
[
b]
1
2
3
4
5
6
7
8
13a
13a
13b
13b
13b
13b
13c
13d
40
100
10
20
40
100
20
100
96
48
48
48
48
24
48
72
14a, 30
14a, 35
14b, –
14b, –
14b, 51
14b, 64
15a, 35
15a, 28
15b, –
[
c]
o-Benzenedisulfonimide (1) was prepared as reported in the litera-
[
[
d]
d]
[13]
ture;
alcohols 2d–f, 9c and 9e were prepared by reduction of
15b, –
[
[
e]
commercially available by Aldrich benzophenones or aceto-
15b, 30
15b, 29
15c, –
[
14]
f]
4 4
phenones with LiAlH or NaBH , as described in the literature.
[
g]
All the other alcohols (2, 9, 11, 13) and all the nitriles 3 were pur-
14c, 60
[
h]
14d, –
15d, –
chased from Aldrich or Fluka. Yields of the pure (GC, GC-MS,
1
13
TLC, H NMR, C NMR) isolated amides 4, 10, 12 and 14 are
reported in Tables 2, 3, 4, and 5, respectively. Structures and puri-
ties of all the products obtained in this research were confirmed by
comparison of their physical (m.p.) and spectroscopic data with
those reported in the literature. Satisfactory microanalyses were ob-
tained for all new compounds.
[
a] Yields refer to the pure products. [b] Dibenzyl ether (0.03 g, 15%
yield) was also isolated. [c] The presence of dibenzyl ether was also
detected by GC-MS, but it disappeared during the reaction. [d] Af-
ter 48 h, only unreacted 13b was detectable by GC-MS. [e] Bis(4-
methylbenzyl) ether (0.03 g, 13% yield) was also isolated. [f] The
presence of bis(4-methylbenzyl) ether was also detected by GC-MS,
but it disappeared during the reaction. [g] Bis(4-methoxyphenyl)-
methane (0.09 g, 40% yield) was also isolated. [h] No traces of 14d
or 15d were detected by GC-MS analysis. 4-Nitrobenzyl acetate
N-(Diarylmethyl)amides 4. General Procedures. Method A (Nitrile
as Solvent): o-Benzenedisulfonimide (1, 10 mol-%, 0.22 g, 1 mmol)
was added to a solution of an alcohol 2 (10 mmol) in a nitrile 3
(
0.11 g, 31% yield) was isolated.
(
5 mL) and the mixture was stirred at the temperature reported in
Table 2. The reactions were monitored by TLC, GC and GC-MS
until the complete disappearance of the alcohols 2 and the ethers
by-product was astonishing, but it could be assumed that
an electrophilic aromatic substitution had occurred, with
the 4-methoxybenzyl cation, reacting with 13c, replacing
6; the reactions time are reported in Table 2. The reaction mixture
was poured into dichloromethane/water (100 mL, 1:1). The aque-
ous layer was separated and extracted with dichloromethane
the CH OH group, which leaves as protonated formalde-
2
hyde. On the other hand, the presence of a strongly elec-
tron-withdrawing group (Table 5, Entry 8) prevented the
(
2ϫ50 mL). The combined organic extracts were washed with
water (2ϫ50 mL), dried with Na SO and concentrated under re-
2
4
formation of 14d. The only product obtained was 4-ni- duced pressure. The crude residues were chromatographed on a
trobenzyl acetate, originating from the nucleophilic ad- short flash column, with elution with petroleum ether/ethyl acetate
dition of 13d to 3a and the hydrolysis of the adduct formed. (9:1) to provide pure amides 4. The aqueous layer and aqueous
washings were collected and evaporated under reduced pressure.
1
After removal of the water, virtually pure ( H NMR) o-benzenedi-
sulfonimide (1) was recovered (about 80% yields in all the reac-
Conclusions
tions) m.p. 192–194 °C (toluene, ref.[ m.p. 192–194 °C).
13]
In this paper the synthetic usefulness of o-benzenedisul-
The recovered 1 was employed in other two catalytic cycles with 2a
fonimide (1) as a catalyst in Ritter-type reactions has been
and 3a under the conditions described above; Table 1 reports the
demonstrated. The target products 4a–o, 10a–f and 12a–e
yields of amide 4a, the yields of recovered 1 and the reaction times.
were obtained in good to excellent yields (average yields
were 81%, 64% and 59%, respectively), while less satisfac-
tory results were obtained for 14a–d (average yield was
N-(Diphenylmethyl-)-3-toluamide (4d): M.p. 158 °C (MeOH), 1
NMR (200 MHz, CDCl , 25 °C): δ = 7.62–7.59 (m, 4 H), 7.45–7.25
m, 10 H), 6.72–6.64 (m, 1 H), 6.46 (d, J = 7.60 Hz, 1 H), 2.41 (s,
H
3
(
40%). Furthermore, in comparison with strong liquid or
1
3
3
1
2
8
H) ppm. C NMR (50 MHz, CDCl
3
, 25 °C): δ = 166.9, 141.7,
solid Brønsted acids, extensively used for research laborato-
ries to chemical manufacturing plants, 1 turned out be a
safe, non-volatile, and non-corrosive catalyst. A further
valuable aspect of the use of 1 is its high solubility in both
organic solvents and water. In particular, its easy recovery
in high yield from the reaction mixture, due to its complete
solubility in water, and its reuse without loss of catalytic
activity in other reactions, is very important, offering econ-
omic and ecological advantages.
38.7, 134.4, 132.6, 128.9, 128.6, 128.0, 127.7, 124.2, 57.5,
+
1.5 ppm. MS (EI): m/z = 301 [M] . C21H19NO (301.39): calcd. C
3.69, H 6.35, N 4.65; found C 83.73, H 6.31, N 4.65.
4
-Acetyl-N-(diphenylmethyl)benzamide (4f): M.p. 183 °C (MeOH),
1
H NMR (200 MHz, CDCl
3
, 25 °C): δ = 7.97 and 7.91 (2 d, 1:1, J
=
8.20 Hz, 4 H), 7.45–7.24 (m, 10 H), 6.79–6.76 (m, 1 H), 6.46 (d,
13
3
J = 7.60 Hz, 1 H), 2.64 (s, 1 H) ppm. C NMR (50 MHz, CDCl ,
2
1
5 °C): δ = 197.0, 165.9, 141.3, 138.3, 132.7, 128.9, 128.7, 127.9,
27.8, 57.8, 27.0 ppm. MS (EI): m/z (%) = 329 [M] . C22H19NO
2
+
(
4
329.40): calcd. C 80.22, H 5.81, N 4.25; found C 80.25, H 5.86, N
.26.
Experimental Section
N-[(4-Nitrophenyl)phenylmethyl]benzamide (4k): M.p. 169–170 °C
1
General Remarks: All reactions were conducted in flasks open to
the air; analytical grade reagents and solvents were used and reac-
tions were monitored by TLC, GC and GC-MS. Mass spectra were
recorded with an HP 5989B mass selective detector connected to
an HP 5890 GC cross-linked methyl silicone capillary column. TLC
were performed on Merck silica gel 60 (70–230 mesh ASTM) and
GF 254, respectively. Flash chromatography was carried out on sil-
(MeOH), H NMR (200 MHz, CDCl
3
, 25 °C): δ = 8.17 and 7.82
(2 d, 1:1, J = 8.60 Hz, 4 H), 7.67–7.25 (m, 10 H), 6.91–6.87 (m, 1
1
3
3
H), 6.47 (d, J = 7.60 Hz, 1 H) ppm. C NMR (50 MHz, CDCl ,
25 °C): δ = 167.0, 149.0, 147.2, 140.2, 133.7, 133.0, 129.4, 128.8,
128.3, 127.9, 127.7, 127.3, 124.0, 57.5 ppm. MS (EI): m/z = 332
+
[M] . C20
H
16
N
2
O
3
(332.36): calcd. C 72.28, H 4.85, N 8.43; found
C 72.29, H 4.88, N 8.44.
434
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 430–436

Reusable Brønsted Acid Catalyst
N-[Bis(4-fluorophenyl)methyl]benzamide (4m): M.p. 177–179 °C N-Benzylamides 14. General Procedure: o-Benzenedisulfonimide (1)
1
(
MeOH), H NMR (200 MHz, CDCl
3
, 25 °C): δ = 7.81–7.78 (m, 2 was added to a solution of a benzyl alcohol 13 (2.0 mmol) in 3a
H), 7.56–7.38 (m, 3 H), 7.27–7.20 (m, 4 H), 7.10–6.98 (m, 4 H), (5 mL) under the conditions given above; the catalyst amounts are
1
3
6
(
1
1
=
.85–6.81 (m, 1 H), 6.38 (d, J = 7.60 Hz, 1 H) ppm. C NMR
reported in Table 5. The mixture was stirred at reflux at the time
reported in Table 4. TLC, GC and GC-MS analyses showed the
presence of two main products, amides 14 and N-benzyl-o-benzene-
disulfonimides 15, besides small amounts of the dibenzyl ethers.
The usual workup provided crude residues that were chromato-
graphed on short flash columns with elution with petroleum ether/
diethyl ether (1:1). The first eluted products were N-benzyl-o-
benzenedisulfonimides 15; the second were amides 14. After re-
1
3
50 MHz, CDCl , 25 °C): δ = 166.8, 162.3 (d, JC,F = 244.5 Hz),
37.3 (d, JC,F = 3.1 Hz), 134.1, 132.1, 129.2 (d, JC,F = 8.1 Hz),
28.8, 127.2, 115.8 (d, JC,F = 21.3 Hz), 56.37 ppm. MS (EI): m/z
4
3
2
+
323 [M] . C20
H
15
F
2
NO (323.34): calcd. C 74.29, H 4.68, F 11.75,
N 4.33; found C 74.27, H 4.68, F 11.74, N 4.37.
In a collateral verification, 1 (10 mol-%, 0.22 g, 1 mmol) was added
to a solution of 2a (1.84 g, 10 mmol) in 3a (5 mL) and the mixture
was stirred at reflux for 2 h. TLC, GC and GC-MS analyses
showed the presence of three product: 2a, 4a and ether 5a. The
reaction was stopped, and the usual workup furnished a crude resi-
due that was chromatographed on a short flash column with elu-
tion with petroleum ether/ethyl acetate (9:1). The first eluted prod-
uct was bis(diphenylmethyl) ether (5a, 0.73 g, 41% yield); the sec-
ond was 2a (0.13 g, 7% yield) and the third was 4a (1.02 g, 46%
yield).
1
moval of the water under reduced pressure, virtually pure ( H
NMR) o-benzenedisulfonimide (1) was recovered (about 80% yield
in all the reactions).
N-(4-Methylbenzyl)-o-benzenedisulfonimide (15b): M.p. 111–112 °C
1
(
toluene), H NMR (200 MHz, CDCl
3
, 25 °C): δ = 8.08–7.97 and
7
.93–7.87 (2 m, 1:1, 4 H), 7.43 and 7.22 (2 d, 1:1, J = 7.80 Hz, 4
13
H), 4.86 (s, 2 H), 2.37 (s, 3 H) ppm. C NMR (50 MHz, CDCl
3
,
2
5 °C): δ = 138.7, 135.6, 135.0, 130.4, 129.8, 128.5, 122.5, 45.5,
+
Method B (without Solvent): o-Benzenedisulfonimide (1, 10 mol-%,
4 2
21.4 ppm. MS (EI): m/z = 323 [M] . C14H13NO S (323.38): calcd.
0
.22 g, 1 mmol) was added to a mixture of alcohols 2 (10 mmol)
C 52.00, H 4.05, N 4.33, S 19.83; found C 52.03, H 4.09, N 4.35,
S 19.82.
and nitriles 3 (10 mmol) and the reactions were monitored by TLC,
GC and GC-MS until the complete disappearance of 2 and ethers
5
furnished crude residues that were virtually pure amides 4. Vir-
tually pure ( H NMR) o-benzenedisulfonimide (1) was also reco-
Supporting Information (see also the footnote on the first page of
this article): Spectroscopic and characterization data of known
products.
; the reaction times are reported in Table 2. The above workup
1
vered (about 80% yield in all the reactions).
Acknowledgments
N-(1-Arylethyl)amides 10. General Procedure: o-Benzenedisulfon-
imide (1, 10 mol-%, 0.22 g, 1 mmol) was added to a solution of
alcohols 9 (10 mmol) in nitriles 3 (5 mL) according to the condi-
tions reported above, and the mixture was stirred at the tempera-
ture reported in Table 3. The reactions were monitored by TLC,
GC and GC-MS until the complete disappearance of 9 and the
corresponding bis(arylethyl) ethers; the reaction times are reported
in Table 3. The usual workup provided crude residues that were
chromatographed on a short flash column, with elution with petro-
leum ether/ethyl acetate (9:1) to provide pure amides 10.
This work was supported by the Ministero dell’Università e della
Ricerca and by the University of Torino.
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Received: September 24, 2008
Published Online: December 9, 2008
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 430–436