Lithium perchlorate mediated three component reaction for the preparation of primary amines

Article abstract of DOI:10.1039/a808424f

In the presence of lithium perchlorate in diethyl ether, LPDE, a three- component reaction between aldehydes, sodium hexamethyldisilazane or lithium hexamethyldisilazane, LHMDS, and different nucleophiles proceeds smoothly to afford primary amines in good yields.

Full text of DOI:10.1039/a808424f

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330 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 330^331y
Lithium Perchlorate Mediated Three Component
Reaction for the Preparation of Primary Aminesy
Mohammad R. Saidi,* Shahrzad Javanshir and
Mohammad M. Mojtahedi
Department of Chemistry, Sharif University of Technology P.O. Box 11356-9516, Teheran,
I.R. of Iran
In the presence of lithium perchlorate in diethyl ether, LPDE, a three-component reaction between aldehydes, sodium
hexamethyldisilazane or lithium hexamethyldisilazane, LHMDS, and different nucleophiles proceeds smoothly to afford
primary amines in good yields.
Addition reactions of carbonyl and related compounds are
the most useful and important reactions in organic
chemistry.1 Also, synthesis of amines by the Mannich
reaction has been extensively studied by organic chemists.
Since the classical Mannich reaction has many limitations,
numerous attempts have been made to overcome these, owing
Table 1 The structure and yields of the primary amines
Entry Aldehyde
Nucleophile
Product
Yield(%)
Ph
NH2
PhCHO
PhCHO
1
2
57
Ph
MgBr
Ph
4a
5
to the importance of the products.2
NC
Ph
NCSiMe3
60
The synthesis of primary amines is of interest due to their
8
NH2
di¡erent uses.6
One approach involves addition of
4b
organometallic reagents to imines, but the low electrophilicity
of the imine carbon has frequently hindered these reactions.
The reactivity of imines has been improved by complexation
with Lewis acids, or by preparation of `masked' imine
derivatives of ammonia. They react with organometallic
reagents followed by the removal of the protecting group
Ph
PhCHO
PhCHO
PhCHO
PhCHO
3
4
5
6
87
43
86
83
BrMg
NH2
4c
Ph
MeLi
LiCH2CN
PhLi
NH2
13
to give primary amines.9
4d
Ph
NC
Recently, we reported the lithium perchlorate mediated one
pot three-component aminosilylation of aldehydes 1, with
lithium hexamethyldisilazane or sodium hexamethyl-
disilazane and a nucleophiles with a silicon protecting group,
for the preparation of trimethylsilyl amines 3, in good
yields,14 Scheme 1.
NH2
4e
Ph
Ph
NH2
4d
NH2
CHO
LiC CPh
74
7
LPDE
RCHO + (Me3Si)2NLi
RCHN(SiMe3)2
O–
[R CH NSiMe3]
MeO
Ph
MeO
4g
1
2
NH2
r.t.
CHO
CHO
2
+
LiC CSi(CH3)3
RCHC CSi(CH3)3
LiC CPh
LiCH2Ph
8
9
30
31
NH2
3
Cl
Ph
Cl
4h
4i
NH2
Scheme 1
On the basis of this idea, in this paper we report a simple
method for the synthesis of several primary amines from
the preformed imines, mediated by lithium perchlorate, which
avoids multistep procedures. Aldehyde 1 reacts with sodium
hexamethyldisilazane or LHMDS in the presence of a 5 M
solution of lithium perchlorate in diethyl ether at r.t. to pro-
duce imine 2, in situ, in about 30 min. Reaction of organ-
olithium and other nucleophiles with 2 at r.t. a¡ords the
corresponding primary amines 4 in good to moderate yields,
Scheme 2.
The structures and the yields of the products are shown in
Table 1. When the reaction was carried out without using
5 M LPDE, compound 4 was produced in very low yields
(up to 10%).
O2N
Ph
O2N
CN
NCSiMe3
10
11
12
60
55
S
S
CHO
S
S
NH2
4j
Bu
BuLi
CHO
NH2
4k
SiMe3
Ph
CHO
CHO
LiC CSiMe3
75
60
Ph
NH2
4l
NH2
CH2SiMe3
In conclusion, we have devised a synthesis for primary
amines by nucleophilic addition of organometallic reagents
to aldimines mediated by 5 M LPDE. Most of the crude
amine products are of su¤cient purity for subsequent use.
BrMgCH2SiMe3
13
S
S
4m
* To receive any correspondence.
Experimental
General.öLiClO4 (Fluka) was dried at 160 8C and 10 1 Torr for
48 h, diethyl ether over Na benzophenone under argon. IR spectra
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 331
r.t.
2
+
R'Li or R'MgBr
RCHR'
NH2
4a–m
S
R =
,
,
,
,
,
O2N
MeO
Cl
R' = Me, Ph, n-Bu, PhCH2, CN, CH2CN, CH2SiMe3, PhC≡C, Me3SiC≡C
Scheme 2
were taken on a Matt Son 1000 Unicam FTIR, 1H and 13C NMR
spectra on Bruker AC 80 spectrometer. All reactions were
performed under argon. Chemicals were purchased from Fluka and
used as received.
Caution: Although we did not have any accidents using LiClO4, it
is advised to dry lithium perchlorate in a hood using a suitable
lab-shield. The ether solution should be freshly prepared and not
stored.
We acknowledge Volkswagen-Stiftung, Federal Republic of
Germany for ¢nancial support to purchase laboratory
chemicals. We also thank the Research Council of the Sharif
University of Technology for its partial ¢nancial support
of this work.
a
Received, 30th October 1998; Accepted, 2nd February 1999
Paper E/8/08424F
Procedure for the Preparation of Primary Amines (Entries 1^13 in
Ta bl e 1).öHexamethyldisilazane, HMDS (3.3 mmol, 0.54 g), was
placed in a two-necked £ask ¢tted with a condenser and a stirring
bar, under argon, 3.5 mmol of sodium hydride (60^65%, after
washing with light petroleum) or 3.3 mmol of methyllithium in diethyl
ether were added, and the mixture was stirred for about 5 min. Then
3 mL solution of 5 M LPDE and 2 mmol of aldehyde were added
via a syringe. After stirring for 30 min, organometallic reagent or
other nucleophile (4 mmol) was added via syringe, and the mixture
stirred for 30 min. Water (10 mL) was added and the product
extracted with ether ꢀ2 Â 10 mL). The organic layer was separated
and extracted with cold 0.5 MHCl solution. Neutralization with a
2.0 M solution of KOH gave the desired product. Further puri¢cation
was by preparative gas chromatography if needed. The structures of
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1
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