A practical synthesis of N-tosylimines of arylaldehydes

Article abstract of DOI:10.1016/S0040-4039(02)02809-5

Synthesis of N-tosylimines of arylaldehydes was carried out by the reaction of arylaldehydes and p-toluenesulfonamide in methylene chloride in the presence of trifluoroacetic anhydride as a dehydrating agent.

Full text of DOI:10.1016/S0040-4039(02)02809-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1231–1234
A practical synthesis of N-tosylimines of arylaldehydes
Ka Young Lee, Chang Gon Lee and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Kwangju 500-757, South Korea
Received 6 November 2002; revised 6 December 2002; accepted 6 December 2002
Abstract—Synthesis of N-tosylimines of arylaldehydes was carried out by the reaction of arylaldehydes and p-toluenesulfonamide
in methylene chloride in the presence of trifluoroacetic anhydride as a dehydrating agent. © 2003 Elsevier Science Ltd. All rights
reserved.
N-Sulfonylimines are important synthetic intermediates
in organic synthesis.1 Various useful methods of prepar-
ing these compounds are known.2 Chemla and co-
workers have reported an easy synthesis of
N-sulfonylimines by the reaction of aldehyde, sulfon-
amide and sodium p-toluenesulfinate in aqueous formic
acid, and subsequent treatment of the generated sulfon-
amide sulfone intermediate with sodium bicarbonate.2a
Jennings and Lovely have used titanium tetrachloride
and triethylamine for the synthesis of N-tosylimines.2b
The synthesis of N-tosylimines from aldehydes and
chloramine-T in the presence of tellurium metal was
reported by Trost and Marrs.2c Synthesis of N-sul-
fonylimines based on the preparation and in situ rear-
rangement of oxime O-sulfinates have been reported.2d
Sisko and Weinreb have reported the reaction of alde-
hydes and N-sulfinyl p-toluenesulfonamide for the in
situ generation of N-tosylimines.2e Georg and co-work-
ers have reported the one-flask conversion of aldehydes
and ketones to N-sulfonylimines by the reaction of
N-trimethylsilylaldimine with various sulfonyl chlo-
rides.2f Most of all, simple condensation between alde-
hydes and sulfonamides appeared most frequently.2b,g
Various reagents and conditions have been used includ-
ing the use of molecular sieves and Amberlyst under
Dean–Stark conditions2g or tetraethyl orthosilicate.2h
Nevertheless, it is important to develop an efficient
method of N-tosylimines under mild conditions by
using readily available reagents.
We were interested in the synthesis of N-sulfonylimines
during our investigations on the chemical transforma-
tions of the Baylis–Hillman adducts of N-tosylimines.3
Basically, major problems for the synthesis of N-sul-
fonylimines might be (1) the cleavage of prepared N-
sulfonylimines into starting materials, aldehydes and
Scheme 1.
Keywords: N-tosylimines; arylaldehydes; trifluoroacetic anhydride; N-tosyl enamines.
* Corresponding author. Fax: +82-62-530-3389; e-mail: kimjn@chonnam.chonnam.ac.kr
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02809-5

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K. Y. Lee et al. / Tetrahedron Letters 44 (2003) 1231–1234
shifted forward by the following trifluoroacetylation
into II. Next step, elimination of trifluoroacetic acid
from II, can occur more easily than the corresponding
dehydration from I. In the reaction mixture, N-tri-
fluoroacetyl tosylamide (4)5 was found in trace amounts
on TLC. In order to examine the involvement of 4, we
prepared 4 from tosylamide and trifluoroacetic anhy-
dride quantitatively (99%).5 However, the reaction of
benzaldehyde and 4 did not give 3a at all in refluxing
CH2Cl2. From the results the mechanism involving 4
was not seemed plausible. The use of methanesulfonyl
chloride (62%) or p-tosyl chloride (52%) instead of
acetic anhydride or trifluoroacetic anhydride did not
show good results. Thus, we prepared some N-
tosylimines from arylaldehydes by using trifluoroacetic
anhydride and the results are summarized in Table 1.
As shown, various kinds of arylaldehydes showed simi-
lar results (83–89% isolated yields).6 However, the reac-
tion of aliphatic aldehydes with acidic a-hydrogen atom
showed different results. The results are shown in Table
2. As shown in entries 1–3, the corresponding N-tosyl
enamines 5a–c were obtained.6–9 For n-hexanal (1j),
major product was obtained via successive aldol con-
densation followed by formation of N-tosylimine.6
sulfonamide, especially in hydrolytic conditions, (2)
limited nucleophilicity of sulfonamide toward alde-
hydes, which makes the equilibrium for the formation
of aminal stage backwards, as a result, requiring strong
acidic conditions in order to eliminate water, (3) side
reactions of aldehydes having acidic a-hydrogen atoms.
In these respects, we focused initially our attention to
find a condition for shifting the equilibrium for the
formation of aminal forwards easily by simply quench-
ing it with acetic anhydride (see, Scheme 1). The use of
acetic anhydride meets our rational approach very well.
The reaction of benzaldehyde (1a) and tosylamide (2a)
in methylene chloride in the presence of acetic anhy-
dride gave the desired benzaldehyde N-tosylimine (3a)
in 81% yield. It is very interesting to note that the use
of acetic anhydride for the synthesis of N-sul-
fonylimines has not been reported.
The same reaction with trifluoroacetic anhydride
showed improved results (88%, entry 1 in Table 1) both
in yield and purity. In Scheme 1, the reaction pathway
is shown with the reaction of benzaldehyde and p-tolue-
nesulfonamide as an example. The equilibrium for the
formation of N-tosyl hemiaminal4 derivative I can be
Table 1. Synthesis of N-tosylimines of arylaldehydes

K. Y. Lee et al. / Tetrahedron Letters 44 (2003) 1231–1234
1233
Table 2. The reaction of aliphatic aldehydes and tosylamide
As a summary we disclosed a facile synthetic method of
N-tosylimines of arylaldehydes by using the simple
concept: elimination of trifluoroacetic acid is easier
than dehydration.
2. Synthesis of N-tosylimines, see: (a) Chemla, F.; Hebbe, V.;
Normant, J.-F. Synthesis 2000, 75 and further references
cited therein. (b) Jennings, W. B.; Lovely, C. J. Tetra-
hedron 1991, 47, 5561; (c) Trost, B. M.; Marrs, C. J. Org.
Chem. 1991, 56, 6468; (d) Boger, D. L.; Corbett, W. L. J.
Org. Chem. 1992, 57, 4777; (e) Sisko, J.; Weinreb, S. M. J.
Org. Chem. 1990, 55, 393; (f) Georg, G. I.; Harriman, G.
C. B.; Peterson, S. A. J. Org. Chem. 1995, 60, 7366; (g)
Vishwakarma, L. C.; Stringer, O. D.; Davis, F. A. Org.
Synth. Coll. Vol. VIII 1993, 546; (h) Love, B. E.; Raje, P.
S.; Williams, T. C., II. Synlett 1994, 493; (i) Suzuki, H.;
Takeda, S.; Hanazaki, Y. Chem. Lett. 1985, 679; (j) Jen-
nings, W. B.; Lovely, C. J. Tetrahedron Lett. 1988, 29,
3725.
Acknowledgements
This work was supported by Korea Research Founda-
tion Grant (KRF-2002-015-CP0215).
3. (a) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Gong, J. H. Synlett
2002, 173; (b) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Kim, H.
S. Tetrahedron Lett. 2001, 42, 3737; (c) Lee, H. J.; Kim, H.
S.; Kim, J. N. Tetrahedron Lett. 1999, 40, 4363; (d) Lee, H.
J.; Seong, M. R.; Kim, J. N. Tetrahedron Lett. 1998, 39,
6223.
4. (a) Ingrassia, L.; Mulliez, M. Synthesis 1999, 1731; (b)
Milenkovic, A.; Fache, F.; Faure, R.; Lemaire, M. Synth.
Commun. 1999, 29, 1535.
5. (a) Nagasawa, H. T.; Smith, W. E.; Kwon, C.-H. J. Org.
Chem. 1985, 50, 4993; (b) McKay, W. R.; Proctor, G. R.
J. Chem. Soc., Perkin Trans. 1 1981, 2435.
6. Typical experimental procedure for the synthesis of 3a: To
a stirred mixture of benzaldehyde (106 mg, 1 mmol) and
p-tosylamide (188 mg, 1.1 mmol) in methylene chloride (5
mL) was added trifluoroacetic anhydride (231 mg, 1.1
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K. Y. Lee et al. / Tetrahedron Letters 44 (2003) 1231–1234
mmol) and heated to reflux for 12 h. The reaction mixture
6.48 (dq, J=10.8 and 1.5 Hz, 1H), 6.66 (d, J=10.8 Hz,
1H), 7.18–7.82 (m, 9H); 13C NMR (CDCl3) l 14.24, 21.52,
119.89, 119.96, 125.37, 126.73, 126.78, 128.39, 129.86,
137.14, 140.59, 143.84. 6: oil; 1H NMR (CDCl3) l 0.81–
0.93 (m, 6H), 1.25–1.34 (m, 8H), 1.39–1.51 (m, 2H), 2.30–
2.39 (m, 4H), 2.43 (s, 3H), 6.48 (t, J=7.5 Hz, 1H), 7.32 (d,
J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 8.46 (s, 1H); 13C
NMR (CDCl3) l 14.22, 14.31, 22.00, 22.80, 22.98, 25.40,
28.97, 29.97, 31.00, 31.89, 128.11, 129.99, 136.27, 140.11,
144.42, 157.93, 174.31.
was poured into cold water and extracted with CH2Cl2.
The organic layers were dried (MgSO4) and evaporated to
afford crude product. Flash column chromatography (hex-
ane/ether=8:1) gave pure 3a as a white solid, 228 mg
1
(88%). H NMR spectroscopy and its melting points were
identical with reported. The purity of 3a was >95%.
Selected spectroscopic data of N-tosyl enamines, 5c-Z and
5c-E, and tosylimine 6 are as follows. 5c-Z: white solid,
mp 151–153°C; 1H NMR (CDCl3) l 1.92 (d, J=1.2 Hz,
3H), 2.45 (s, 3H), 6.10 (d, J=10.9 Hz, 1H), 6.17 (dq,
J=10.9 and 1.2 Hz, 1H), 6.91–7.70 (m, 9H); 13C NMR
(CDCl3) l 21.59, 21.89, 118.39, 121.19, 126.85, 127.43,
127.64, 129.16, 129.80, 136.85, 138.37, 143.75. 5c-E: oil;
1H NMR (CDCl3) l 1.87 (d, J=1.5 Hz, 3H), 2.41 (s, 3H),
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