Lithium perchlorate mediated three-component preparation of primaryaminoesters

Article abstract of DOI:10.3390/70100072

A three-component reaction between an aldehyde, metallated hexamethyldisilazane and a functionalized organozinc compound proceeded smoothly in the presence of LiClO₄ in diethyl ether to afford primary amino esters in good yields.

Full text of DOI:10.3390/70100072

Molecules 2002, 7, 72-74
molecules
ISSN 1420-3049
http://www.mdpi.org
Lithium Perchlorate Mediated Three-Component Preparation
of Primary Aminoesters
Mohammad R. Saidi* and Najmoddin Azizi
Department of Chemistry, Sharif University of Technology P. O. Box 11356-9516, Teheran, Iran
*Author to whom correspondence should be addressed; e-mail: saidi@sharif.edu
Received: 18 September 2001; in revised form 6 December 2001 / Accepted: 14 December 2001 /
Published: 31 January 2002
Abstract:
A
three-component reaction between an aldehyde, metallated
hexamethyldisilazane and a functionalized organozinc compound proceeded smoothly in
the presence of LiClO in diethyl ether to afford primary amino esters in good yields.
4
Keywords: Primary aminoesters; Lithium perchlorate; Mannich reaction.
Introduction
Recently, we reported the lithium perchlorate mediated one pot three-component aminoalkylation
of aldehydes, 1, with (trimethylsilyl)dialkylamines, 2, or N-(trimethylsilyl)-N-alkylamines 3, and
functionalized organozinc compounds, for the preparation of tertiary aminoesters, 4, and secondary
aminoesters, 5, respectively (Scheme 1){1,2].
Scheme 1
LiClO4
1) BrZnCH CO Et
R
OEt
2
2
RCHO
1
+
Me SiNR '
3
2
ether, r.t.
2
) H O
2
2
4
NR ' O
2
R = Ar or Me CH
2
LiClO4
1) BrZnCH CO Et
R
OEt
2
2
RCHO
+
Me SiNHR'
3
ether, r.t.
2
) H O
1
3
2
NHR' O
5
R = Ar or Me CH
R' = Ph or Bu
2

Molecules 2002, 7
73
Results and Discussion
Alkylzinc reagents are generally unreactive toward aldehydes. For such reactions to proceed,
special circumstances are required, involving either highly reactive organozinc regents, such as α-zinc
ester, or activation in the presence of Lewis acids [3]. In this paper, we would like to report that the
reaction of aldehydes, 1, with sodium or lithium hexamethyldisilazane, 6, at r.t., in the presence of a
5M solution of lithium perchlorate in diethyl ether produces the imine 7, in situ, in about 30 min. The
subsequent reaction of 7 with the bromoalkylzinc ester BrZnCH COOEt in diethyl ether at room
2
temperature then afforded the corresponding primary aminoesters, 8, in good yields (Scheme 2).
Scheme 2
Ar
LiClO4
1) BrZnCH CO Et
R
OEt
2
2
ArCHO + (Me Si) NNa
3
2
ether, r.t. H
NSiMe3
2) H O
2
NH2
O
1
6
7
8
The structures of the primary aminoesters prepared are shown below. When the reaction was
carried out in diethyl ether or dichloromethane solution without using LiClO , products 8 were
4
produced in low yield after long reactions (ca. 40% of 7a after stirring for 24 hours at r. t.).
OEt
N
OEt
OEt
NH2
O
NH2
O
NH2
O
8
a
8b
8c
Acknowledgments
We thank “Volkswagen-Stiftung, Federal Republic of Germany” for financial support towards the
purchase of chemicals and equipment. M.R. Saidi thanks the Ministry of Science, Research and
Technology of Iran for partial financial support.
Experimental
General
Chemicals were purchased from Fluka and used as received, except for LiClO , which was dried at
4
-
1
1
60°C and 10 Torr for 48 h. Ether was dried over Na/benzophenone under argon. IR spectra were
1
taken on a Mattson 1000 Unicam FTIR, HNMR spectra were recorded on Bruker AC 80 or Bruker
TM
5
00 MHz Ultra Shield instruments. All reactions were performed under argon.

Molecules 2002, 7
74
Caution: Although we have not experienced any accidents while using LiClO , the authors advise that
4
this reagent should always be dried in a hood equipped with a suitable lab-shield.
General Procedure for the Preparation of Primary Aminoesters 8:
Hexamethyldisilazane (3.5 mmol, 0.24 mL) was placed under argon in two-necked flask fitted with
a condenser and a stirring bar. Diethyl ether (3 mL) and 3.7 mmol of sodium hydride (60-65%, after
washing with light pet. ether) were added, and the mixture was stirred for about 30 min. Then 3 mL of
a 5M solution of lithium perchlorate in diethyl ether and 2 mmol of aldehyde were added via syringe.
After stirring for 30 min., the bromoalkylzinc ester, BrZnCH COOEt, (3.5 mmol) was added, and the
2
mixture was stirred for an additional 2.0 hours. Water (10 mL) was then added and the product was
extracted with dichloromethane (2x10 mL). The organic layer was separated and extracted with cold
0.5 M HCl solution. Neutralization with 2.0 M KOH solution gave the desired products. Further
purification was done by preparative gas chromatography if needed. All products described had
structures in accordance with their spectroscopic data.
Spectroscopic data
-1 1
8
a, oil, (65%), IR (neat), νmax 3538 (NH ), 1730 (C=O) cm ; H-NMR (CDCl ): δ 1.20 (t, 3H, J 7.2
2 3
OCH CH ), 2.00 (br. s, 2H, NH ), 2.60 (d, 2H, J 6.7 CH CH), 4.10 (q, J 7.2, 2H, OCH CH ), 5.10 (t, J
2
3
2
2
2
3
6
.7, 1H, CH CH), 7.20 (s, 5H, Ar-H) [4].
2
-1 1
8
b, oil, (78%), IR (neat), νmax 3400 (NH ), 1725 (C=O) cm ; H-NMR (CDCl ): δ 1.20 (t, 3H, J 7.1
2 3
OCH CH ), 2.20 (br. s, 2H, NH ), 2.60 (d, 2H, J 6.7 CH CH), 4.10 (q, J 7.1, 2H, OCH CH ), 4.40 (t, J
2
3
2
2
2
3
6
.7, 1H, CH CH), 7.10-7.30 (m, 1H, Ar-H), 7.60-7.80 (m, 1H, Ar-H), 8.40-8.60 (m, 2H, Ar-H).
2
-1 1
8
c, oil, (60%), IR (neat), νmax 3389 (NH ), 1723 (C=O) cm ; H-NMR (CDCl ): δ 1.10 (t, 3H, J 7.4
2 3
OCH CH ), 2.00 (br. s, 2H, NH ), 2.70 (d, 2H, J 5.7 CH CH), 3.40 (m, 1H, CH CH), 4.10 (q, J 7.4,
2
3
2
2
2
2
H, OCH CH ), 6.20-6.60 (m, 2H, CH=CH), 7.10-7.45 (5H, Ar).
2 3
References
1. Saidi, M. R.; Khalaji, H. R.; Ipaktschi, J. J. Chem. Soc., Perkin Trans. 1, 1997, 1983-1986.
2. Saidi, M. R.; Azizi, N.; Zali-Boinee, H. Tetrahedron, 2001, 57, 6829-6832.
3. Ochiai, H.; Nishihara, T.; Tamaru, Y.; Yoshida, Z. J. Org. Chem., 1988, 53, 1343-1345.
4. Cole, D. Tetrahedron, 1994, 50, 9517-9582.
Sample availability: available from the authors.
2002 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes
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