The first example of saccharin-lithium bromide catalysis: Direct synthesis of N-tosylimines from alcohols

Article abstract of DOI:10.1002/adsc.201000193

The first procedure to access N-tosylimines directly from alcohols under mild and neutral conditions is reported. The protocol involves saccharin-lithium bromide-catalyzed oxidation of alcohols to aldehydes/ketones with chloramine-T followed by their condensation with the in situ generated oxidation by-product p-toluenesulfonamide in the same reaction vessel to afford N-tosylimines in 40-90% overall yields. The present work opens up a new and efficient synthetic route to N-tosyimines directly from alcohols in a one-pot procedure.

Full text of DOI:10.1002/adsc.201000193

COMMUNICATIONS
DOI: 10.1002/adsc.201000193
The First Example of Saccharin-Lithium Bromide Catalysis:
Direct Synthesis of N-Tosylimines from Alcohols
a
a
a,
Rajesh Patel, Vishnu P. Srivastava, and Lal Dhar S. Yadav *
a
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
Fax : (+91)-532-246-0533; phone: (+91)-532-250-0652; e-mail: ldsyadav@hotmail.com
Received: March 11, 2010; Published online: June 30, 2010
Abstract: The first procedure to access N-tosyl-
imines directly from alcohols under mild and neu-
and multi-step procedures. Recently, a few examples
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
of the catalytic N-alkylation of sulfonamides with
benzylic alcohols have been reported to proceed via
N-sulfonylimine formation, but in none of these cases
tral conditions is reported. The protocol involves
saccharin-lithium bromide-catalyzed oxidation of al-
cohols to aldehydes/ketones with chloramine-T fol-
lowed by their condensation with the in situ gener-
ated oxidation by-product p-toluenesulfonamide in
the same reaction vessel to afford N-tosylimines in
[
17]
have the sulfonylimines been isolated.
All the methods available for the synthsis of N-sul-
fonylimines utilize an aldehyde or a ketone as one of
the starting materials. However, some of the alde-
hydes are volatile, toxic, or unstable, especially be-
cause of aerial oxidation. Thus, in many cases alde-
hydes must be purified just before their use because
the presence of other products affects not only the
concentration of the active aldehyde but also the im-
purities often interfere with chemical reactions involv-
ing the aldehyde. Alcohols are usually more stable,
less volatile, and less toxic than the corresponding al-
dehydes and, meanwhile, the oxidation of alcohols is
an important method for forming aldehydes. More-
40–90% overall yields. The present work opens up
a new and efficient synthetic route to N-tosyimines
directly from alcohols in a one-pot procedure.
Keywords: alcohols; catalysis; chloramine-T; oxida-
tion; saccharin-lithium bromide; N-sulfonylimines
Imines bearing electron-withdrawing N-substituents over, one-pot multi-step reactions are of increasing
[
1]
are useful intermediates in organic synthesis. N-Sul- academic, economical and ecological interest because
fonylimines have been increasing in importance in the they address fundamental principles of synthetic effi-
[2]
last two decades as they are one of the few types of ciency and reaction design.
[
3]
electron-deficient imines that are stable enough to
Several methods for the formation of imines by
be isolated but reactive enough to undergo addition coupling alcohols with amines in the presence of an
[
4]
[18]
reactions. They are used in numerous reactions such oxidant have been reported but, to the best of our
[
5]
[6]
as nucleophilic addition, hetero-Diels–Alder, or knowledge, there is no report on the formation of N-
ene reactions. In addition, N-sulfonylimines are ex- sulfonylimines starting directly from alcohols. This is
cellent precursors for the preparation of aziridines
and oxaziridines. Thus, various synthetic routes to sulfonamides requiring activation of the condensing
[7]
[
8]
presumably because of the weak nucleophilicity of
[9]
N-sulfonylimines have been developed, which include aldehydes/ketones and operationally special condi-
[
10]
Lewis acid-catalyzed reactions of sulfonamides with tions to combine the oxidation and condensation
[
11]
aldehydes, rearrangement of oxime O-sulfinates,
steps in a domino process. Thus, it is an interesting
tellurium-mediated reaction of aldehydes with chlora- target of investigation, which prompted us to develop
[
12]
mine-T,
reaction of N-TMS-imines with sulfonyl a convenient one-pot synthesis of N-tosylimines di-
13]
[
chloride,
microwave-facilitated,
acid-catalyzed rectly from alcohols as an endeavour in continuation
[19]
[
14]
direct condensations, and utilization of acetic anhy- of our work on one-pot multi-step syntheses.
dride as dehydrating and acylation agent.
We
[
15]
reasoned that chloramine-T would be a well suited ox-
The direct condensation of carbonyl compounds idant for the conversion of alcohols to the corre-
with sulfonamides is used as the straightforward route sponding aldehydes or ketones for the present study
[
16]
for the preparation of N-sulfonylimines, which usu- because it leaves TsNH as a by-product, which could
2
ally requires harsh acidic conditions, high tempera- be utilized in the subsequent step to afford N-tosyl-
tures and often dehydrating apparatus. Furthermore,
some other methods need cumbersome experimental
ACHTUNGTRENUNNGi mines in a one-pot operation (Scheme 1).
1610
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1610 – 1614

The First Example of Saccharin-Lithium Bromide Catalysis:
Scheme 1. Direct synthesis of N-tosylimines from alcohols.
Scheme 2. A plausible mechanism for the conversion of an alcohol to an N-sulfonylimine.
In order to realize the envisaged protocol, we inves-
The present optimized synthesis of N-sulfonylimine
tigated the direct synthesis of N-sulfonylimines via ox- 3a involves the stirring of equimolar mixture of
idative coupling of benzyl alcohol (5 mmol) with benzyl alcohol and chloramine-T in DCM using sac-
chloramine-T (5 mmol) using the saccharin-LiBr cata- charin-LiBr (30 mol%) as the catalyst at room tem-
lyst system in dichloromethane (DCM). In this reac- perature for 3 h followed by addition of molecular
tion chloramine-T oxidizes benzyl alcohol to benzal- sieve (4ꢁ) and refluxing for 9 h. After several minute
dehyde and itself is reduced to p-toluenesulfonamide. of stirring at room temperature, the reaction mixture
The freshly generated aldehyde and sulfonamide con- became thick then it turned yellowish to red and in
dense to form N-tosylimines in the same reaction the course of completion of the reaction it became
vessel (Scheme 1). Plausibly, the alcohol is oxidized to yellowish at reflux. As shown in Table 3, the scope of
the corresponding aldehyde by in situ generated N- the reaction of alcohols with chloramine-T was ex-
bromosaccharin as depicted in Scheme 2.
plored. For benzyl alcohol and substituted benzyl al-
A systematic study was undertaken to screen the cohols containing either electron-withdrawing or elec-
catalyst system for the synthesis of N-sulfonylimine 3a tron-donating substituents, or heteroaryl alcohols
with various imides and metal halides (Table 1). It (Table 3, entries 1–9 and 14) the reactions proceeded
was found that among the catalysts tested, saccharin- smoothly and afforded N-sulfonylimines 3 in moder-
LiBr gave the best result (Table 1 entry 6), whereas ate to high yields. For the nitro- and chloro-substitut-
the other structurally analogous imides gave compara- ed benzyl alcohols, the reaction proceeded compara-
tively low yields (Table 1, entries 4 and 5). This is tively slower and gave moderate yields (Table 3, en-
probably due to more electrophilic nature of N-bro- tries 2, 3 and 8). Similarly, ortho-substituted benzyl al-
mosaccharin compared with N-bromosuccinimide and cohols gave relatively low yields (Table 3, entries 7
N-bromophthalimide. Out of metal halides tested, and 8).
LiBr showed better catalytic activity than KBr
A variety of aliphatic alcohols were also examined
(
Table 1, entries 3 and 6), presumably due to the to explore the scope of this reaction. Primary alcohols
higher Lewis acidity of lithium ions. Likewise, LiCl showed good reactivity and gave good yields of the
and LiI were found to be far less effective than LiBr corresponding imines (Table 3, entries 10 and 11). In
under the same reaction conditions. On the other case of secondary alcohols, the reaction proceeded
hand, among several suitable solvents tested, DCM slower and gave low yields of the corresponding ket-
was found to be most suitable (Table 2, entry 4).
ACHTUNGTRNENUNGi mines (Table 3, entries 12 and 13).
Adv. Synth. Catal. 2010, 352, 1610 – 1614
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1611

Rajesh Patel et al.
COMMUNICATIONS
[a]
Table 1. Optimization of catalyst for the synthesis of N-sulfonylimines.
[b]
[c]
Entry
Catalyst [mol%]
Time [h]
Yield [%] of
3
a
4a
5
1
2
3
4
5
6
7
8
9
succinimide-KBr [30 mol%]
phthalimide-KBr [30 mol%]
saccharin-KBr [30 mol%]
succinimide-LiBr [30 mol%]
phthalimide-LiBr [30 mol%]
saccharin-LiBr [30 mol%]
KBr [50 mol%]
LiBr [50 mol%]
LiBr [100 mol%]
saccharin [40 mol%]
saccharin-LiBr [20 mol%]
saccharin-LiBr [40 mol%]
26
25
20
16
14
12
24
24
24
22
16
12
30
32
35
70
78
90
–
40
56
–
50
52
62
15
17
5
44
10
15
53
15
6
52
53
63
17
18
6
8
13
17
56
18
7
1
1
1
0
1
2
65
90
[
[
[
a]
Reaction conditions: benzyl alcohol (5 mmol), chloramine-T (5 mmol), DCM (3 mL), 4ꢁ mol sieves (200 mg).
Mol% of each catalyst.
Yields of the isolated pure compounds.
b]
c]
Table 2. Optimization of solvent.
LiBr (30 mol%) portionwise with stirring at room tempera-
ture. After stirring the reaction mixture for 3 h at room tem-
perature, 4ꢁ molecular sieve (200 mg) was added and
stirred for 9–37 h at reflux temperature. The reaction prog-
ress was monitored by TLC. Upon completion (Table 3), the
solvent was evaporated under reduced pressure, the residue
dissolved in 10 mL THF, filtered and n-hexane (5–10 mL)
was added to afford a crude product. The crude product was
recrystallized/from THF-n-hexane (1:1) to afford analytical-
ly pure N-sulfonylimines 3. The oily compounds (Table 3,
entries 11–13) were purified by flash chromatography (silica
[a]
Entry
Solvent
Time [h]
Yield [%]
1
2
3
4
5
6
acetonitrile
1,4-dioxane
THF
DCM
toluene
DMF
18
23
17
12
24
30
70
65
58
90
68
trace
gel, Et O-hexane, 3:2). The structures of the products were
2
1
confirmed by comparison of their mp, TLC, IR or H NMR
data with authentic samples obtained commercially or pre-
pared by the literature methods.
[
a]
Yield of isolated and purified compound 3a.
[10–12,16d,f ]
Since all the products are known, the spectral data of only
some typical compounds are given below:
N-Benzylidene-p-toluenesulfonamide: white solid; yield:
In summary, we have developed the first saccharin-
LiBr catalyzed convenient synthesis of N-sulfonyl-
imines directly from alcohols. The protocol involves
oxidation of alcohols to aldehydes or ketones with
chloramine-T followed by their condensation with the
in situ formed oxidation by-product p-toluenesulfon-
9
1
0%; mp 111–1128C; IR (KBr): n =1650, 1570, 1380,
max
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
À1
1
326, 1160 cm ; H NMR (400 MHz, CDCl , TMS): d=9.04
3
(
s, 1H), 7.92–7.87 (m, 4H), 7.61 (t, J=7.5 Hz, 1H), 7.47 (t,
J=7.6 Hz, 2H), 7.34 (d, J=8.2 Hz, 2H), 2.45 (s, 3H);
1
3
C NMR (100 MHz, CDCl , TMS): d=23.3, 127.4, 129.1,
3
ACHTUNGTRENNUNGa mide to afford N-tosylimines in a one-pot operation. 130.2, 131.1, 131.9 133.2, 139.8, 145.7, 171.1; MS (EI): m/z=
+
The present work opens up a new and efficient one- 259 [M ].
pot synthetic route to N-sulfonylimines directly from
alcohols.
N-(p-Chlorobenzylidene)-p-toluenesulfonamide:
white
solid; yield: 69%; mp 174–1768C; IR (KBr): n =1652,
1565, 1370, 1320, 1163 cm ; H NMR (400 MHz, CDCl3,
TMS): d=9.02 (s, 1H), 7.90–7.87 (m, 4H), 7.49 (d, J=
max
À1
1
1
3
7
.4 Hz, 2H), 7.36 (d, J=7.1 Hz, 2H), 2.46 (s, 3H); C NMR
(
1
2
100 MHz, CDCl , TMS): d=23.2, 128.5, 129.7, 130.1, 131.3,
Experimental Section
3
32.7 135.2, 140.2, 145.6, 170.2; MS (EI): m/z=295 [(M+
+ +
) ], 293 [M ].
General Procedure for One-Pot Synthesis of N-
Sulfonylimines Directly from Alcohols
N-(p-Methoxybenzylidene)-p-toluenesulfonamide: white
solid; yield: 87%; mp 128–1298C; IR (KBr): n =1665,
1563, 1375, 1325, 1168 cm ; H NMR (400 MHz, CDCl3,
max
À1
1
In a mixture of alcohol 1 (5 mmol), chloramine-T (5 mmol)
and saccharin (30 mol%) in 3–5 mL of DCM was added
TMS): d=8.97 (s, 1H), 7.91–7.88 (m, 4H), 7.36 (d, J=
1612
asc.wiley-vch.de
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1610 – 1614

The First Example of Saccharin-Lithium Bromide Catalysis:
[a]
Table 3. One-pot synthesis of N-sulfonylimines.
[b]
[c,d]
Entry
Alcohol
Product 3
Time [h]
Yield [%]
mp [8C]
Ref.
[
[
[
[
[
[
[
[
[
[
[
[
[
[
10]
1
2
3
4
5
6
7
8
9
C H CH OH
C H CH=NTs
12
25
25
19
20
20
24
27
16
19
24
35
40
17
90
60
69
85
87
88
70
63
89
82
80
40
43
83
111–112
141–142
174–176
181–183
128–129
78–79
140–141
133–134
110–112
101–102
oil
6
5
2
6
5
16d]
10]
m-O NC H CH OH
m-O NC H CH=NTs
2
6
4
2
2 6 4
p-ClC H CH OH
p-ClC H CH=NTs
6 4
6
4
2
12]
p-BrC H CH OH
p-BrC H CH=NTs
6
4
2
6 4
12]
p-MeOC H CH OH
p-MeOC H CH=NTs
6 4
6
4
2
16f]
16f]
16d]
15]
m-MeOC H CH OH
m-MeOC H CH=NTs
6
4
2
6 4
o-BrC H CH OH
o-BrC H CH=NTs
6
4
2
6
4
o-ClC H CH OH
o-ClC H CH=NTs
6
4
2
6 4
p-MeC H CH OH
p-MeC H CH=NTs
6 4
6
4
2
12]
1
1
1
1
1
0
1
2
3
4
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(CH ) CCH OH
ACHTUNGTNERNUNG( CH ) CCH=NTs
3
3
2
3 3
16d]
11]
n-C H CH OH
n-C H CH=NTs
3 7
3
7
2
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(CH ) CHOH
A
H
U
G
R
N
N
(CH ) C=NTs
oil
oil
99–100
3
2
3 2
11]
cyclohexanol
cyclohexyl=NTs
2-furylCH=NTs
16d]
2-furylCH OH
2
[
[
[
a]
See Experimental Section for general procedure.
Total stirring time.
b]
c]
[10–12,16d,f]
All the products are known compounds
and were characterized by comparison of their mp, TLC, IR and
1
H NMR data with those of authentic samples.
[
d]
Yields of the isolated pure compounds.
8
3
1
.0 Hz, 2H), 6.99 (d, J=8.8 Hz, 2H), 3.91 (s, 3H), 2.45 (s,
[5] a) T. Ooi, Y. Uematsu, K. Maruoka, J. Am. Chem. Soc.
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13
H); C NMR (100 MHz, CDCl , TMS): d=23.1, 56.7,
3
16.5, 126.1, 128.7, 130.5, 135.1, 139.6, 145.2, 165.1, 170.3;
+
MS (EI): m/z=289 [M ].
2,2-Dimethyl-N-tosylpropan-1-imine: white solid; yield:
8
1
1
2%; mp 101–1028C; IR (KBr): nmax =1630, 1327,
[6] a) O. Garcia-Mancheno, R. Gomez-Arrayas, J. C. Car-
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À1
1
165 cm ; H NMR (400 MHz, CDCl3, TMS): d=9.02 (s,
,
H), 7.83 (d, J=8.7 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 2.44
1
3
(
s, 3H), 1.2 (s, 9H); C NMR (100 MHz, CDCl , TMS): d=
3
2
3.4, 27.8, 33.2, 128.9, 131.3, 139.3, 145.1, 169.8; MS (EI):
[7] M. Yamanaka, A. Nishida, M. Nakagawa, Org. Lett.
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m/z=239 [M ].
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N-Tosylpropan-2-imine: yellowish oil; yield: 40%; IR
neat): nmax =1646, 1330, 1153 cm ; H NMR (400 MHz,
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À1
1
(
CDCl , TMS): d=7.84 (d, J=8.6 Hz, 2H), 7.34 (d, J=
3
8
.6 Hz, 2H), 2.51 (s, 3H), 2.49 (s, 3H), 2.44 (s, 3H);
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1
3
C NMR (100 MHz, CDCl , TMS): d=18.1, 23.2, 27.9,
3
+
1
29.0, 130.2, 140.1, 145.2, 170.1; MS (EI): m/z=211 [M ].
4
777.
[
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Acknowledgements
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Adv. Synth. Catal. 2010, 352, 1610 – 1614