Synthesis of α-aminoorthoesters from O-tosylhydroximates

Article abstract of DOI:10.1081/SCC-120004265

The abstraction of the acid hydrogen of O-tosylhydroximates 1 by sodium ethylate, then nucleophilic attack of the excess of sodium ethylate at the more hindred carbond atom of azirine 2 and aziridine 3 intermediates to give the α-aminoorthoesters (35-45%

Full text of DOI:10.1081/SCC-120004265

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SYNTHESIS OF α-AMINOORTHOESTERS FROM O-
TOSYLHYDROXIMATES
Néji Besbes a , Abdelghani Bel Hadj Amor b & Bel gacem Baccar c
a Département de Chimie, Faculté des Sciences de Monastir, Monastir, 5019, Tunisie
b Institut Préparatoire des Etudes Ingénieur de Nabeul, Nabeul, 8000, Tunisie
c Département de Chimie, Faculté des Sciences de Tunis, Tunis, 1020, Tunisie
Version of record first published: 16 Aug 2006.
To cite this article: Néji Besbes , Abdelghani Bel Hadj Amor & Bel gacem Baccar (2002): SYNTHESIS OF α-AMINOORTHOESTERS
FROM O-TOSYLHYDROXIMATES, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 32:11, 1709-1713
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SYNTHETIC COMMUNICATIONS, 32(11), 1709–1713 (2002)
SYNTHESIS OF a-AMINOORTHOESTERS
FROM O-TOSYLHYDROXIMATES
Neji Besbes,1, Abdelghani Bel Hadj Amor,2 and
*
3
Bel gacemBaccar
1Departement de Chimie, Faculte des Sciences de
Monastir, 5019, Monastir, Tunisie
2Institut Preparatoire des Etudes Ingenieur de
Nabeul, 8000, Nabeul
3Departement de Chimie, Faculte des Sciences
de Tunis, 1020, Tunis
ABSTRACT
The abstraction of the acid hydrogen of O-tosylhydroximates
1 by sodium ethylate, then nucleophilic attack of the excess of
sodium ethylate at the more hindred carbond atom of azirine 2
and aziridine 3 intermediates to give the ꢀ-aminoorthoesters
(35–45% yields). The ꢀ-aminoorthoester 4a is transformed
into ꢀ-iminoorthoesters 5a (63% yield) and ꢀ-amidoortho-
ester 6a (65% yield).
Key Words: ꢀ-Amidoorthoesters; ꢀ-Aminoorthoesters; Azi-
ridines; Azirinines; ꢀ-Iminoorthoesters; Nucleophilic ring
opening; O-tosylhydroximates
*Corresponding author. Fax: 216 77 500 278; E-mail: Besbes_neji@hotmail.com
1709
Copyright & 2002 by Marcel Dekker, Inc.
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1710
BESBES, BEL HADJ AMOR, AND BACCAR
Scheme 1.
We have previously reported that the imidate derivatives gave oxazo-
lines,[1] oxazoles,[2] benzoxazines,[3] quinoleines[4] and triazoles[5] by reaction
with organometallic compounds and hydrazines. We have also shown that
N-2-cyanophenylethylbenzimidate was transformed into aminoquinoline by
the action of LDA being the base abstracting the acid hydrogen and com-
pleting the reaction (Scheme 1).[6]
We have studied in this paper the effect of the replacement of the
cyanophenyl group by well-leaving groups, and we used another base
such as the sodium ethylate. So, the reaction of O-tosylhydroximates
1a–d with an excess of sodium ethylate in ethanol at room temperature
for six days gave the ꢀ-aminoorthoesters 4a–d with 35–45% overall yields
(Scheme 2).
Scheme 2.
To explain the unexpected product 4, we may suggest that in the first
step of the reaction, the ethylate anion abstracted the acid hydrogen of the
methylene group of O-tosylhydroximate 1 to give an intermediate, which
cyclised into azirine 2. The same nucleophile attacked the latter instable
azirine 2 at the more hindred carbon atom, then attacked the aziridine 3
and yielded the ꢀ-aminoorthoester 4 (Scheme 2).

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a-AMINOORTHOESTERS
1711
However, when we treated the O-acetyl, O-trimethylsilyl and
O-oxodiethoxyphosphorylhydroximates by sodium ethylate we regenerated
the starting hydroximates, these three latter products were derived by the
specific nucleophilic attack at the more electrophile center. The abstraction
of the hydrogen atom of O-tosyloximes followed by cyclization into azirines
then ring opening of the corresponding aziridines into ꢀ-aminoketones by
an excess of sodium ethylate also have been reported by Neber.[7]
Moreover, Graham[8] has shown that the reaction of N-chloroimino-
esters with sodium ethylate yielded ꢀ-aminoorthoesters. The acid hydrolysis
of the latter products gave ꢀ-aminoesters, the water molecule attacked the
orthoester group. In the present investigation, we have treated the com-
pound 4a with benzaldehyde and acetylchloride. The products 5a (63%)
and 6a (65%) were formed by nucleophilic attack of the amine group of
4a at the carbonyl group of these two precedent reagents (Scheme 3).
Scheme 3.
From these results, we can conclude that the synthesis of ꢀ-amino-
orthoesters appears to depend on the degree of leaving group activation.
EXPERIMENTAL
General: Melting points were determined with Buchi apparatus and
are uncorrected. IR spectra were run on a Perkin Elmer IR-681 infrared
1
spectrometer in CHCl3 solution. H NMR spectra were recorded on a Jeol
EM (60 MHz) in CDCl3 solution. Chemical shifts are expressed in ppm
with reference to TMS as an internal standard coupling constants given in
Hz. Splitting patterns are designated as s, singlet; d, doublet; t, triplet;
q, quartet; m, multiplet.

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1712
BESBES, BEL HADJ AMOR, AND BACCAR
Synthesis of a-aminoorthoesters 4 from O-tosylhydroximates 1: To a
stirred solution of 1 (1 mol) in dry ether (50 ml) was added a solution of
sodium in absolute ethanol (100 ml) at 0ꢀC, and the reaction mixture was
stirred at room temperature for 6 days. The sodium tosylate was filtered and
the solvent was evaporated under normal pressure. The residue was distilled
under reduced pressure to yield (35–45%) of 4.
Orthoester 4a: B.p.0.5 ¼ 35ꢀC. Yield, 45%. IR: 3390, 3315, 1630 (NH2),
1
1605 (C¼C), 1285, 1120 (C–O). H NMR: 1.10 (t, J ¼ 5, 9H), 1.74 (s, 2H),
3.55 (q, J ¼ 5, 6H), 4.06 (s, 1H), 6.80–7.90 (m, 5H).
Orthoester 4b: B.p.0.5 ¼ 90ꢀC. Yield, 40%. IR: 3390, 3310, 1660 (NH2),
1
1610 (C¼C), 1280, 1110 (C–O). H NMR: 1.25 (t, J ¼ 5, 9H), 2.10 (s, 2H),
2.83 (s, 3H), 3.56 (q, J ¼ 5, 6H), 4.53 (s, 1H), 7.00–8.00 (m, 4H).
Orthoester 4c: B.p.0.3 ¼ 110ꢀC. Yield, 40%. IR (KBr): 3380, 3310, 1660
(NH2), 1635 (C¼C), 1280, 1120 (C–O). 1H NMR: 1.16 (t, J ¼ 5, 9H), 1.73 (s,
2H), 3.60 (q, J ¼ 5, 6H), 4.10 (s, 1H), 7.30 (m, 4H).
Orthoester 4d: B.p.0.1 ¼ 124ꢀC. Yield, 35%. IR: 3420, 3360, 1660
1
(NH2), 1640 (C¼C), 1280, 1120 (C–O). H NMR: 1.20 (t, J ¼ 5, 9H), 2.10
(s, 2H), 3.60 (q, J ¼ 5, 6H), 4.35 (s, 1H), 7.17–7.34 (m, 3H).
Reaction of 4a with benzaldehyde: A mixture of 4a (5.1 g, 0.02 mol),
benzaldehyde (2.12 g, 0.02 mol), BaO (2.75 g, 0.02 mol) and dry xylen (20 ml)
was refluxed for 18 h. The precipate of BaO, H2O was filtered and the xylen
was evaporated. The crude product was distilled to give the yellow liquid of
5a.
Orthoester 5a: B.p.18 ¼ 120ꢀC. Yield, 63%. IR: 1670 (C¼N), 1660
(C¼C), 1280, 1120 (C–O). 1H NMR: 1.10 (t, J ¼ 5, 9H), 3.50 (q, J ¼ 5,
6H), 4.10 (s, 1H), 4.45 (s, 1H), 7.20 (m, 10H).
Reaction of 4a with acetyl chloride: To a solution of 4a (5.10 g,
0.02 mol) in Et3N (3 g, 0.03 mol) was added a solution of acetyl chloride
(1.57 g, 0.02 mol) in dry ether (30 ml) at 0ꢀC. The reaction mixture was
stirred at ambient temperature for 24 h, and then the precipate of Et3N,
HCl was filtered. The excess of Et3N and ether was removed in vacuo to
afford the product as white crystal of 6a.
Orthoester 6a: M.p.: 70ꢀC. Yield, 65%. IR: 3440 (N–H), 1665 (C¼O),
1
1600 (C¼C), 1280, 1120 (C–O). H NMR: 1.10 (t, J ¼ 5, 9H), 1.19 (s, 3H),
3.50 (q, J ¼ 5, 6H), 5.20 (s, 1H), 6.40 (s, 1H), 7.20 (m, 5H).
REFERENCES
1. Bel Lassoued, M.; Gaudemar, M.; Hajjem, B.; Baccar, B. Bull. Soc.
Chim. Belg. 1986, 95, 65.
2. Hajjem, B.; Baccar, B. Synthetic Comm. 1992, 21, 1521.

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a-AMINOORTHOESTERS
1713
3. Hajjem, B.; Chihi, A.; Baccar, B. Synthetic Comm. 1992, 22, 295.
4. Hajjem, B.; El Efrit, M.L.; Chihi, A.; Baccar, B. Indian J. Chem. 1995,
34(B), 330.
5. Kammoun, M.; Hajjem, B.; Zantour, H.; Baccar, B. J. Soc. Chim.
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Burgard, A. Ann. 1932, 493, 281.
8. Graham, W.H. Tetrahedron Lett. 1969, 27, 174.
Received in the Netherlands May 30, 2001

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