Facile cleavage of Si-C bonds during the sol-gel hydrolysis of aminomethyltrialkoxysilanes - A new method for the methylation of primary amines

Article abstract of DOI:10.1002/ejoc.200400079

The reaction of chloromethyltriethoxysilane with (1R,2R)-bis(methylamino) cyclohexane (1) afforded the corresponding bis-silylated compound 2. The sol-gel hydrolysis of 2 did not give the expected bridged silsesquioxane owing to quantitative Si-C-bond cleavage. Instead, silica and (1R,2R)-bis(dimethylamino) cyclohexane (3) were obtained. This reaction was exploited to propose a new route for the methylation of amines. Such methylation reaction of amines could be extended to other amines and provides a new method for the selective monomethylation of primary amines. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400079

FULL PAPER
Facile Cleavage of Si؊C Bonds during the Sol-Gel Hydrolysis of
Aminomethyltrialkoxysilanes ؊ A New Method for the Methylation
of Primary Amines
[a]
[a]
[a]
[a]
¨
Augustin Adima, Catherine Bied, Joel J. E Moreau,* and Michel Wong Chi Man
Keywords: Alkylation / Amines / Condensation / Hydrolysis / Sol-gel processes
The reaction of chloromethyltriethoxysilane with (1R,2R)-bi-
s(methylamino)cyclohexane (1) afforded the corresponding
bis-silylated compound 2. The sol-gel hydrolysis of 2 did not
give the expected bridged silsesquioxane owing to quantitat-
ive Si−C-bond cleavage. Instead, silica and (1R,2R)-bis(dime-
thylamino)cyclohexane (3) were obtained. This reaction was
exploited to propose a new route for the methylation of
amines. Such methylation reaction of amines could be ex-
tended to other amines and provides a new method for the
selective monomethylation of primary amines.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
lysts, we examined the possibility of synthesizing a related
material from (1R,2R)-bis[methyl(triethoxysilylmethyl)ami-
The sol-gel hydrolysis-condensation of organoalkoxysil- no]cyclohexane (2) with only one carbon alkylene spacer
anes has until now been used as a smooth method to between the nitrogen and the silicon atoms. The replace-
achieve hybrid silicas.[1] In this context, multifunctional ment of the propylene by a methylene spacer was expected
organosilanes
with
bridging
organic
units, to enhance the rigidity of the hybrid chiral network and
(RO)3SiϪRЈϪSi(OR)3, (RЈ ϭ organic bridging unit, R ϭ thereby induce better selectivity properties to the asymmet-
Me, Et) were rapidly revealed to be interesting precursors ric catalytic material. Unexpectedly, during the hydrolysis-
to afford a new type of hybrid materials known as bridged condensation step, significant cleavage of the SiϪC bonds
silsesquioxanes.[2,3] This interesting route allows a high occurred, leading to the formation of silica (SiO2) and
loading of organic fragments in silicas and materials chem- leaching of (1R,2R)-bis(dimethylamino)cyclohexane (3). We
ists soon realized the importance of this molecular ap- report here our studies on the scope of this cleavage reac-
proach for the design of new materials. A wide variety of tion and its possible use in the synthesis of methylated am-
organosilylated compounds have led to materials with tar- ines.
geted properties.[4] Recently we reported the transcription
of the chiral properties of the organic moiety to the hybrid
material with the formation of right- and left-handed helical
Results and Discussion
fibers.[5] The use of bridging organic units capable of self-
association by hydrogen bonding allowed the formation of
supramolecular assemblies and afforded a general method
Synthesis and Hydrolysis of (1R,2R)-Bis[methyl(triethoxy-
silylmethyl)amino]cyclohexane (2)
for the nanostructuration and the shaping of hybrid sil-
The bis-silylated compound 2 was obtained in 68% yield
by the reaction of an excess of chloromethyltriethoxysilane
icas.[6] We have already succeeded in the immobilization of
chiral trans-(1R,2R)-diaminocyclohexane derivatives in a
(3 molar equivalents) with (1R,2R)-bis(methylamino)cy-
silica network.[7] The formation of [(1R,2R)-bis(triethoxysi-
clohexane (1; Scheme 1).[8] The hydrolysis-condensation of
solutions of 2 was carried out in ethanol at room tempera-
ture with NH4F as catalyst (0.1 mol %). A gel formed
lylpropylamino)cyclohexyl]rhodium complexes, followed by
sol-gel hydrolysis, gave a catalytic hybrid material which
proved to be an efficient enantioselective catalyst for the
within one minute and then solubilized after one day, lead-
asymmetric reduction of prochiral ketones. In an effort to
ing to a new solution. Then, a second gelation occurred
improve the efficiency of these novel heterogeneous cata-
within three days affording a stable gel. After aging for one
week it was crushed and the resulting powder was washed
[a]
´
´ ´
Laboratoire de Chimie Organometallique, Heterochimie
with diethyl ether and dried under vacuum for one day at
60 °C.
´
´
Moleculaire et Macromoleculaire, UMR CNRS 5076, Ecole
´
Nationale Superieure de Chimie de Montpellier,
8, rue de l’Ecole Normale, 34296 Montpellier Cedex 05, France
Fax: ϩ33-4- 67147212
This solid material was analyzed by FT-IR and 13C and
29Si solid-state NMR spectroscopy, and elemental analysis.
E-mail: jmoreau@cit.enscm.fr
2582
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400079
Eur. J. Org. Chem. 2004, 2582Ϫ2588

A New Method for the Methylation of Primary Amines
FULL PAPER
Scheme 1. Preparation and hydrolysis of the bis-silylated molecule 2
Unexpectedly, the 29Si NMR spectrum of this solid pre- related SiϪC bond cleavage has already been observed in
dominantly exhibits signals characteristic of SiO4 substruc- analogous phosphorus compounds in the presence of protic
tures (Q3 and Q4) at δ ϭ Ϫ100 and Ϫ109 ppm, respectively, solvents such as MeOH or H2O;[9] it is thought to involve
and only a low intensity signal centered at δ ϭ Ϫ71 ppm a nucleophilic attack of the oxygen atom at silicon. More-
can be assigned to the expected CSiO3 (T3) substructures over, in the case of the quaternary silylammonium salt
(Figure 1).
Ph3SiϪCH2Nϩ(CH3)2(CH2Ph), Sato et al.[10] have also de-
scribed the nucleophilic attack of the hydride ion on the
SiϪC bond of the ammonium ion leading to the cleavage
of this bond and formation of Ph3SiH.
From these results it seems that the reaction may proceed
according to the following mechanism (Scheme 2). The
hydrolysis of the (aminomethyl)trialkoxysilane 4 affords
the silanol 5. Due to the acidity of the silanol groups, a
quaternary ammonium salt 6 forms. Related zwitterionic
organosilicates of the type RMe2NCH2SiF4 or
R2NϪ(CH2)nϪSi(OR)4 (n ϭ 1, 3) stable in dry media have
already been reported.[11] A nucleophilic attack of SiϪOϪ
at the silicon atom of the ammonium salt then leads to the
cleavage of the SiϪC bond with formation of the am-
monium ylide 7 and a siloxane-bridged compound 8. The
rapid isomerization of 7 gives the dimethylamine 9.
Figure 1. Solid state 29Si NMR spectrum of solid material obtained
upon hydrolysis of 2
The occurrence of such a reaction during the hydrolysis
of 2 prevents the preparation of a hybrid material by a sol-
gel process as it selectively leads to the methylated amino
derivative 3. Therefore, we decided to explore the scope of
this reaction leading to methylated amines from silylated
precursors as it may be of interest for the selective prep-
aration of monomethylated amines, especially because silica
is the only by-product of this reaction. We examined the
influence of several factors on the hydrolysis of aminome-
thylsilanes and then explored some use of the reaction for
the methylation of primary amines.
The presence of these Q units indicates a high amount of
SiϪC cleavage during the hydrolysis-condensation pro-
cess,[3a] whereas the T3 unit represents some residual or-
ganic fragments still covalently bonded to silicon. From this
observation a significant loss of organics is expected. This
loss was confirmed by elemental analysis of the dried gel,
which gave an N to Si ratio of 0.33 instead of the ratio of
1 expected in the absence of SiϪC cleavage.
For a better understanding of this phenomenon, we de-
cided to recover the organic compound formed during the
hydrolysis process. The hybrid material was washed several
times with diethyl ether and the solvents were evaporated
from the filtrate. The 1H and 13C NMR spectra of the crude
residue proved that the compound formed was actually
Influence of the Substituents at Silicon and of the Structure
of the Amine
We first studied the influence of the number of alkoxy
(1R,2R)-bis(dimethylamino)cyclohexane (3). It should be groups linked to the silicon atom on the rate of the SiϪC
noted that the SiϪC bond cleavage only occurs in the pres- bond cleavage. For this purpose, we prepared two diamino-
ence of water and that it was not observed in dry EtOH. A cyclohexane derivatives 10 and 11 (Scheme 3) and com-
Eur. J. Org. Chem. 2004, 2582Ϫ2588
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A. Adima, C. Bied, J. J. E. Moreau, M. Wong Chi Man
FULL PAPER
Scheme 2. Mechanism of the SiϪC bond cleavage by hydrolysis of (aminomethyl)silanes
1
pared their reactivity upon hydrolysis with that of com- monitored by H NMR spectroscopy. In the case of com-
pound 2 (Table 1). Compounds 10 and 11 were prepared pound 10, bearing three CH3 substituents at the silicon
following the same method used for the preparation of 2.
atom, no SiϪC bond cleavage occurred at room tempera-
ture. After heating for two days at 120 °C, only 10% of
compound 3 was obtained. When a methyl group was re-
placed by an ethoxy group (compound 11), a conversion
rate of 28% was observed after three days of reaction at
room temperature, whereas in the case of the compound 2,
with three ethoxy groups at silicon, the reaction proceeded
more rapidly (85% conversion under the same conditions).
These results demonstrate that the number of ethoxy groups
at silicon greatly influences the rate of the SiϪC bond-cleav-
age: a faster reaction occurs when the electrophilicity of the
Si atom is enhanced.
Scheme 3. Influence of the substituents at silicon on the hydrolysis
of (aminomethyl)silanes
We then studied the influence of the structure of the
amine on the reaction. We prepared the two derivatives 12
and 13 (Scheme 4) and performed their hydrolysis under the
same conditions as those previously used for 2.
Table 1. Hydrolysis of amines 2, 10, 11, 12 and 13
Compound Temperature Reaction time (d) Conversion (%)
2
10
11
12
13
20 °C
120 °C
20 °C
20 °C
20 °C
3
2
3
3
3
85
10
28
52
26
The hydrolysis reaction was performed on these three de-
rivatives at room temperature in the presence of three equiv-
alents of H2O with EtOH as solvent and the reaction was
Scheme 4. Structures of the silylated amines 12 and 13
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Eur. J. Org. Chem. 2004, 2582Ϫ2588

A New Method for the Methylation of Primary Amines
FULL PAPER
1
The reactions were followed by H NMR spectroscopy.
We first carried out the reactions in two steps, isolating
This study shows that the reaction goes faster for the bis- the (triethoxysilyl)methylamine intermediates 15, which
silylated compound 2 than for 12 or 13 (Table 1). For the were then hydrolyzed in a second step to afford the mono-
amine 13, the steric hindrance may explain the low amount methylamines 16, leading to overall yields of between 47
of SiϪC cleavage during the hydrolysis of this compound.
and 64%. In the case of diaminocyclohexane (14a) a mix-
ture of the mono- (15a) and the bis-silylated compounds
was obtained; 15a could be separated from the bis-silylated
compound by distillation.[7a,7c]
Selective Monomethylation of Primary Amines
We finally explored whether this reaction could lead to
selective monomethylation of primary amines. Various
methods for the monomethylation of primary amines have
been described in the literature,[12] but they often give poor
yields and selectivities leading to polyalkylations. We there-
fore studied the application of the sol-gel hydrolysis of (ami-
nomethyl)triethoxysilanes in organic synthesis, particularly
for the methylation of primary amines using (chloromethyl)-
triethoxysilane. The main advantages of this reaction are
that it may be performed under mild conditions (low tem-
perature and water as reactant) and it gives only silica as
by-product, which can easily be removed by filtration.
To explore the scope of this new route, we used the fol-
lowing primary amines: diaminocyclohexane, aminocy-
clohexane, benzylamine, aniline and an amino ester (Phe-
Ala-OMe). These amines 14 were first treated with chloro-
methyltriethoxysilane and then hydrolyzed to the corre-
sponding methylated amines 16 (Scheme 5). The yields ob-
tained are given in Table 2.
Taking into account that the silica by-product can easily
be removed by simple filtration, the direct one-pot synth-
eses of the methylated compounds 16b, 16d and 16e, with-
out isolation of the corresponding intermediates 15b, 15d
and 15e, was performed. In the case of the amines 14d and
14e, the yields were significantly improved to 80% in the
case of aniline and 88% for the amino ester instead of 50%
and 47% overall yields, respectively (Table 2). When ben-
zylamine (14c) was used as substrate, the one-pot reaction
gave a mixture of compounds: the expected monomethyl-
benzylamine, dimethylbenzylamine and ortho-methylben-
zylamine; the latter results from a rearrangement of the sily-
lated intermediate as already reported in the case of benzyl
trialkylammonium salts.[13]
Compared to the other methods usually used for the
methylation of amines, the procedure we describe here al-
lows the selective preparation, under mild conditions, of the
monomethylated derivative and avoids the formation of po-
lymethylated products.[12] This selectivity is due to the use
of (chloromethyl)triethoxysilane as a bulky methylating ag-
ent.
Conclusion
The bis-silylation of (1R,2R)-bis(methylamino)cyclohex-
ane has been achieved by the reaction with (chloromethyl)-
triethoxysilane. The hydrolysis of this compound did not
give the expected bridged silsesquioxane. Instead, predomi-
nant SiϪC bond cleavage was observed, even though the
reaction was performed under mild conditions. This cleav-
age leads to the corresponding methylated amine and silica.
Owing to the facile elimination of silica by simple filtration,
this reaction has been exploited for the synthesis of selective
monomethylated primary amines in a one-pot reaction.
Scheme 5. Methylation of primary amines 14 via (aminomethyl)tri-
ethoxysilanes 15
Table 2. Preparation of monomethylated amines 16 via (amino-
methyl)triethoxysilanes 15
Experimental Section
Materials and General Information: All the reactions were per-
formed under nitrogen atmosphere using Schlenk tube techniques.
The solvents were distilled under nitrogen over P2O5 or Mg turn-
ings before use. Commercially available compounds were purchased
from Aldrich, Acros, Gelest or Lancaster and they were used as
received without further purification. Optically active (1R,2R)-di-
aminocyclohexane was obtained enantiomerically pure from the
commercial racemic cis/trans mixture according to Jacobsen’s
method.[14] (Chloromethyl)triethoxysilane was prepared by reaction
of (chloromethyl)trichlorosilane with ethanol in the presence of tri-
ethylamine in an ethereal solution.[15] 1H and 13C NMR spectra in
solution were recorded on a Bruker AC-200 spectrometer in
[a]
Without isolation of the silylated intermediate 15.
Eur. J. Org. Chem. 2004, 2582Ϫ2588
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A. Adima, C. Bied, J. J. E. Moreau, M. Wong Chi Man
FULL PAPER
CDCl3. Chemical shifts (δ, ppm) are relative to tetramethylsilane.
IR spectra were determined with a PerkinϪElmer 1000 FTIR spec-
(dd, 4 H, CH2ϪSi), 2.26 (s, 6 H, CH3ϪN), 2.36Ϫ2.37 (m, 2 H,
CHϪN) ppm. 13C NMR (200 MHz, CDCl3): δ ϭ Ϫ1.3 (SiϪCH3),
trometer. Mass spectra were measured on a JEOL MS-DX 300 24.9 (CH2ϪCH2ϪCH), 25.6 (CH2ϪCHϪN), 40.2 (NϪCH3), 44.8
mass spectrometer. Elemental analyses were carried out by the Ser-
vice Central de Microanalyse du CNRS in Vernaison (France). Op-
tical rotations were measured on a PerkinϪElmer polarimeter 241.
(NϪCH2ϪSi), 66.3 (CHϪN) ppm. 29Si NMR (200 MHz, CDCl3):
δ ϭ Ϫ0.8 ppm. C16H38N2Si2 (314.26): calcd. C 61.14, H 12.10, N
8.91; found C 61.76, H 12.22, N 9.00.
Preparation of 11: The same protocol as above was used, with 1
(7 g, 50 mmol), (chloromethyl)ethoxydimethylsilane (22.6 g,
150 mmol) and dry triethylamine (15.2 g, 150 mmol). Yield: 14 g
Preparation of 2: Compound 1 was prepared in two steps as already
described.[7a,7c] Compound 1 (6 g, 42 mmol), (chloromethyl)tri-
ethoxysilane (26.8 g, 126 mmol) and dry triethylamine (12.7 g,
126 mmol) were placed into a glass tube. The tube was then sealed
under vacuum and placed in an oven at 130 °C with iron protec-
tion. After 18 hours the tube was taken out from the oven and
opened at room temperature. The residue was placed in a 100 mL
flask, washed with dry pentane and filtered. After evaporation of
the solvent, the obtained yellow, viscous liquid was distilled to give
2 as a pale-yellow liquid. Yield: 14 g (68%). B.p.0.009 ϭ 137 °C.
[α]2D0 ϭ Ϫ15.4 (c ϭ 0.4, CHCl3). 1H NMR (200 MHz, CDCl3): δ ϭ
1
(75%). B.p.0.02 ϭ 120 °C. H NMR (200 MHz, CDCl3): δ ϭ 0.11
(s, 12 H, CH3ϪSi), 1.09Ϫ1.19 (m, 4 H, CH2ϪCH2ϪCHϪNH),
1.15 (t, 18 H, CH3ϪCH2), 1.64Ϫ1.75 (m, 4 H, CH2ϪCHϪN), 2.05
(dd, 4 H, NϪCH2ϪSi), 2.22 (s, 6 H, CH3ϪN), 2.25Ϫ2.31 (m, 2 H,
CHϪN), 3.60 (q, 12 H, CH2ϪO) ppm. 13C NMR (200 MHz,
CDCl3):
δ
ϭ
Ϫ1.73 (SiϪCH3), 18.5 (CH3ϪCH2), 24.8
(CH2ϪCH2ϪCH), 25.8 (CH2ϪCHϪN), 39.9 (NϪCH3), 44.1
(NϪCH2ϪSi), 58.2 (CH2ϪO), 66.5 (CHϪN) ppm. C18H42N2O2Si2
(374.71): calcd. C 57.75, H 11.22, N 7.48; found C 58.27, H 11.51,
N 7.67.
1.00Ϫ1.12 (m,
4 H, CH2ϪCH2ϪCHϪN), 1.16 (t, 18 H,
CH3ϪCH2ϪO), 1.61Ϫ1.72 (m, 4 H, CH2ϪCHϪN), 2.05Ϫ2.34 (m,
2 H, CHϪN, 4 H, NϪCH2ϪSi), 2.17 (s, 3 H, CH3ϪNH), 2.26 (s,
6 H, CH3ϪN), 3.76 (q, 12 H, CH2ϪO) ppm. 13C NMR (200 MHz,
CDCl3): δ ϭ 18.2 (CH3ϪCH2), 24.2 (CH2ϪCH2ϪCHϪN), 25.8
(CH2ϪCHϪN), 38.8 (NϪCH2ϪSi), 39.3 (CH3ϪN), 58.2
(CH2ϪO), 65.8 (CHϪN) ppm. 29Si NMR (200 MHz, CDCl3): δ ϭ
Ϫ50.1 ppm. MS [FAB (ϩ)]: m/z (%) ϭ 495 (12) [M ϩ1].
C22H50N2O6Si2 (494.32): calcd. C 53.41, H 10.18, N 5.66; found C
53.44, H 10.20, N 5.68.
Preparation of 12: The same protocol as above was used, with
NϪmethylaminocyclohexane (5 g, 44 mmol), (chloromethyl)tri-
ethoxysilane (5.4 g, 44 mmol) and dry triethylamine (4.5 g,
44 mmol). Yield: 12 g (94%). B.p.0.025
(200 MHz, CDCl3): 1.07Ϫ1.27
ϭ
80 °C. 1H NMR
(m, H,
δ
ϭ
6
CH2ϪCH2ϪCHϪNH), 1.15 (t, 9 H, CH3ϪCH2), 1.54Ϫ1.75 (m, 5
H, CH2ϪCHϪN), 2.01 (s, 2 H, NϪCH2ϪSi), 2.26 (m, 3 H,
CH3ϪN), 3.80 (q, 6 H, CH2ϪO) ppm. 13C NMR (200 MHz,
CDCl3): δ ϭ 18.2 (CH3ϪCH2), 26.0 (CH2ϪCH2ϪCH2ϪCHϪN),
Preparation of 3 by Hydrolysis of 2: The bis-silylated compound 2
(3 g, 6 mmol) in dry ethanol (6 mL) was placed in a glass tube
whilst stirring at room temperature. Distilled water (18 mmol) and
NH4F 1  (6 µL, 0.1% mol) were then added. A gel formed after
1 min, disappeared after 24 h and a new stable gel formed after 3
days. After 1 week, the gel was crushed and the powder obtained
was washed with diethyl ether, filtered and dried under vacuum at
60 °C during 24 h to yield a white powder corresponding to the
xerogel (0.97 g).
26.4
(CH2ϪCH2ϪCHϪN),
27.8
(CH2ϪCHϪN),
37.9
(NϪCH2ϪSi), 40.9 (CH3ϪN), 58.5 (CH2ϪO), 64.9 (CHϪN) ppm.
C14H31NO3Si (289.21): calcd. C 58.83, H 10.72, N 4.84; found C
59.18, H 10.99, N 4.93.
Preparation of 13: The same protocol as above was used, with pip-
eridine (10 g, 117.6 mmol), (chloromethyl)triethoxysilane (25 g,
117.6 mmol) and dry triethylamine (12 g, 117.6 mmol). Yield:
1
28.5 g (90%). B.p.0.02 ϭ 90 °C. H NMR (200 MHz, CDCl3): δ ϭ
1.19 (t, 9 H, CH3ϪCH2), 1.31Ϫ1.45 (m, 2 H, CH2ϪCH2ϪCHϪN),
1.48Ϫ1.58 (m, 4 H, CH2ϪCH2ϪN), 1.92 (s, 2 H, NϪCH2ϪSi),
2.30Ϫ2.34 (m, 4 H, CH2ϪN), 3.80 (q, 6 H, CH2ϪO) ppm. 13C
Identification of 3: The hybrid gel (0.35 g) was introduced into a
10 mL flask and placed under vacuum at 150 °C. The flask was
then cooled to Ϫ100 °C. After 2 hours of distillation, a yellow
liquid (0.07 g) corresponding to 3 was collected at room tempera-
ture; the residual solid weighed 0.22 g.
NMR (200 MHz, CDCl3):
δ
ϭ
18.1 (CH3ϪCH2), 23.7
(CH2ϪCH2ϪCHϪN), 26.2 (CH2ϪCH2ϪN), 44.8 (NϪCH2ϪSi),
58.1 (CH2ϪO), 58.4 (CH2ϪN) ppm. 29Si NMR (200 MHz,
CDCl3): δ ϭ Ϫ50.1 ppm.
Liquid: 1H NMR (200 MHz, CDCl3): δ ϭ 1.04Ϫ1.23 (m, 4 H,
CH2ϪCH2ϪCHϪN), 1.67Ϫ1.83 (m, 4 H, CH2ϪCHϪN), 2.24 (s,
12 H, CH3ϪN), 2.28Ϫ2.37 (m, 2 H, CHϪN) ppm. 13C NMR
General Procedure for the Preparation of 15: The amine 14 (11.67 g,
102 mmol) and (chloromethyl)triethoxysilane (10.87 g, 51 mmol)
were placed in a glass tube. The tube was then sealed under vacuum
and placed in a drying oven at 87 °C with an iron protection. After
18 hours the tube is taken out from the oven and opened at room
temperature. The residue was placed in a 100 mL flask, washed
with dry pentane and filtered. After evaporation of the solvent, the
obtained yellow, viscous liquid was distilled to give 15.
(200 MHz, CDCl3):
δ ϭ 22.9 (CH2ϪCH2ϪCHϪN), 25.6
(CH2ϪCHϪN), 38.8 (NϪCH2ϪSi), 40.1 (CH3ϪN), 63.8
(CHϪN) ppm.
Residual Solid: FT-IR (KBr): ν˜ ϭ 3427, 1096 cmϪ1 29Si CP-MAS
.
NMR: δ ϭ Ϫ92.6 (Q2), Ϫ102.3 (Q3), Ϫ110 (Q4) ppm. SiO2 (59.97):
calcd. Si 46.66, O 53.33; found Si 43.00, O 45.75.
Preparation of 10: Compound 1 (6 g, 42 mmol), (chloromethyl)tri-
15a: Yield: 65%. B.p.0.01 ϭ 97 °C. 1H NMR (200 MHz, CDCl3):
methylsilane (15.5 g, 126.7 mmol) and dry triethylamine (12.8 g, δ ϭ 1.10Ϫ1.20 (m, 4 H, CH2ϪCH2ϪCHϪN), 1.13 (t, 9 H,
126.7 mmol) were placed in a glass tube. The tube was then sealed
under vacuum and placed in a drying oven at 130 °C with an iron
protection. After 18 hours the tube was taken out from the oven
and opened at room temperature. The residue was placed in a
CH3ϪCH2), 1.57Ϫ1.76 (m, 4 H, CH2ϪCH2ϪNH2), 1.97Ϫ2.17 (m,
4 H, CH2ϪCHϪN, CHϪNH2), 2.01 (s, 2 H, NϪCH2ϪSi),
2.57Ϫ2.62 (m, 1 H, NH), 3.80 (q, 6 H, CH2ϪO) ppm. 13C NMR
(200 MHz, CDCl3): δ ϭ 18.2 (CH3ϪCH2), 25.2 (CH2ϪCHϪNH),
100 mL flask, washed with dry pentane and filtered. After evapor- 25.3 (CH2ϪCH2ϪCHϪNH), 30.3 (CH2ϪCHϪNH), 30.4
ation of the solvent, the obtained yellow, viscous liquid was dis- (CH2ϪCHϪNH), 35.6 (NϪCH2ϪSi), 54 (CHϪNH2), 58.6
tilled. Yield: 10 g (76%). B.p.0.009 ϭ 105 °C. H NMR (200 MHz, (CH2ϪO), 67.2 (CHϪNH) ppm. 29Si NMR (200 MHz, CDCl3):
CDCl3): δ ϭ 0.04 (s, 18 H, CH3ϪSi), 1.04Ϫ1.09 (m, 4 H, δ ϭ Ϫ50.2 ppm. C13H30N2O3Si (290.20): calcd. C 53.79, H 10.74,
CH2ϪCHϪCHϪNH), 1.66Ϫ1.78 (m, 4 H, CH2ϪCHϪN), 2.04 N 9.65; found C 55.45, H 10.6, N 9.95.
1
2586
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 2582Ϫ2588

A New Method for the Methylation of Primary Amines
FULL PAPER
1
15c: Yield: 71%. B.p.0.01 ϭ 105 °C. H NMR (200 MHz, CDCl3): a 100 mL flask, washed with dry pentane and filtered. After evap-
δ ϭ 1.24 (q, 9 H, CH3ϪCH2), 1.30 (m, 1 H, NH), 2.16 (s, 2 H,
oration of the solvent, the obtained yellow, viscous liquid was re-
NϪCH2ϪSi), 3.79 (s, 2 H, C6H5ϪCH2ϪNH), 3.86 (t, 6 H, fluxed in a mixture of water (2.9 mL) and ethanol (10 mL) for 2
CH2ϪO), 7.28Ϫ7.31 (m, 5 H, C6H5) ppm. 13C NMR (200 MHz, days. The residue was then filtered and concentrated to give the
CDCl3):
(C6H5ϪCH2ϪN), 58.6 (CH2ϪO), 126 (Caryl-H), 128 (Caryl-H), 140 16b: Yield: 68%. H NMR (200 MHz, CDCl3): δ ϭ 1.05Ϫ1.25 (m,
(Caryl) ppm. 29Si NMR (200 MHz, CDCl3): δ ϭ Ϫ50.2 ppm.
H, CH2ϪCH2ϪCH2ϪCHϪN), 1.58Ϫ1.82 (m, H,
δ ϭ 18.3 (CH3ϪCH2), 33.4 (NϪCH2ϪSi), 57.7 pure methylated amine.
1
6
4
15d: Yield: 80%. B.p.0.01 ϭ 97 °C. 1H NMR (200 MHz, CDCl3): CH2ϪCNϪCH2), 2.25Ϫ2.35 (m, 1 H, NϪCH), 2.39 (s, 3 H,
δ ϭ 1.29 (t, 9 H, CH3ϪCH2), 2.60 (s, 2 H, NϪCH2ϪSi), 3.90 (q,
6 H, CH2ϪO), 6.60Ϫ6.75 (m, 3 H, C6H5), 7.16Ϫ7.31 (m, 2 H,
CH3N) ppm. 13C NMR (200 MHz, CDCl3): δ ϭ 24.6 (CH2), 25.8
(CH2ϪCH2ϪCH2), 32.8 (CH2ϪCHϪN), 33.2 (CH3ϪNH), 54.9
C6H5) ppm. 13C NMR (200 MHz, CDCl3): δ ϭ 18.8 (CH3ϪCH2), (CHϪN) ppm.
28.2 (NϪCH2ϪSi), 59.4 (CH2ϪO), 113 (Caryl-H), 117.6 (Caryl-H), 16d: Yield: 80%.
129.6 (Caryl-H), 150.6 (Caryl) ppm. 29Si NMR (200 MHz, CDCl3):
δ ϭ Ϫ51.0 ppm. C13H23NO3Si (269.15): calcd. C 57.90, H 8.60, N
5.19; found C 57.96, H 8.56, N 5.27.
16e: Yield: 88%.
1
[1] [1a]
15e: Yield: 67%. B.p.0.01 ϭ 115 °C. H NMR (200 MHz, CDCl3):
C. J. Brinker, G. W Scherer, Sol-Gel Science: the Physics
δ ϭ 1.17 (t, 9 H, CH3ϪCH2O), 1.42 (s, 1 H, NH), 2.06 (dd, 2 H,
NHϪCH2ϪSi), 2.89 (s, 2 H, C6H5ϪCH2ϪNH), 3.43 (t, 1 H, CH),
3.60 (s, 3 H, CH3ϪO), 3.73 (q, 6 H, CH2ϪO), 7.13Ϫ7.20 (m, 5 H,
C6H5) ppm. 13C NMR (200 MHz, CDCl3): δ ϭ 18.2 (CH3ϪCH2),
32.2 (NHϪCH2ϪSi), 39.3 (CarylϪCH2), 51.4 (CH3ϪO), 58.6
and Chemistry of Sol-Gel Processing, Academic Press, San Di-
ego, 1990. [1b]C. Sanchez, F. Ribot, New J. Chem. 1994, 18,
[1c]
1007Ϫ1047.
Organic/Inorganic Hybrid Materials. MRS
Symp. vol. 519 (Eds. R. M. Laine, C. Sanchez, C. J. Brinker, E.
Giannelis), 1998. [1d] Organic/Inorganic Hybrid Materials. MRS
Symp. vol. 628 (Eds. R. M. Laine, C. Sanchez, C. J. Brinker),
2000.
(CH2ϪO), 66.3 (CH), 126.5 (Caryl-H), 128.3 (Caryl-H), 129.2 (Caryl
-
H), 137.6 (Caryl), 174.8 (CO) ppm. 29Si NMR (200 MHz, CDCl3):
δ ϭ Ϫ51.5 ppm. C17H29NO5Si (355.18): calcd. C 57.45, H 8.22, N
3.94; found C 56.55, H 7.74, N 4.36.
[2] [2a]
K. J. Shea, D. A. Loy, O. W. Webster, Chem. Mater. 1989,
[2b]
1, 512Ϫ513.
Chem. Soc. 1992, 114, 6700Ϫ6710.
Chem. Rev. 1995, 95, 1431Ϫ1442.
K. J. Shea, D. A. Loy, O. W. Webster, J. Am.
[2c]
D. A. Loy, K. J. Shea,
[3] [3a]
´
Preparation of 16 by Hydrolysis of 15: Dry ethanol (10 mL), the
silylated amine 15 (9.6, 33 mmol) and distilled water (1.8 g,
99 mmol) were introduced into a 50 mL flask. The reaction me-
dium was then aged at 60 °C for 2 days. The solid formed was
separated by filtration, washed with acetone and concentrated un-
der vacuum. The product 16 was obtained as a yellow liquid.
R. J. P. Corriu, J. J. E. Moreau, P. Thepot, M. Wong Chi
Man, Chem. Mater. 1992, 4, 1217Ϫ1224. [3b] R. J. P. Corriu, D.
Leclercq, Angew. Chem. 1996, 108, 1524Ϫ1540; Angew. Chem.
Int. Ed. Engl. 1996, 35, 1420Ϫ1436.
[4] [4a]
U. Schubert, New J. Chem. 1994, 18, 1049Ϫ1058. [4b] H. W.
Oviatt, K. Shea, S. Kalluri, Y. Shi, W. H. Steier, L. R. Dalton,
[4c]
Chem. Mater. 1995, 7, 493Ϫ498.
B. Lebeau, S. Brasselet, J.
1
16a: Yield: 98%. H NMR (200 MHz, CDCl3): δ ϭ 1.10Ϫ1.21 (m,
[4d]
Zyss, C. Sanchez, Chem. Mater. 1997, 9, 1012Ϫ1021.
S.
4 H, CH2ϪCH2ϪCHϪNH2), 1.66Ϫ1.99 (m, 4 H, CH2ϪCH),
2.19Ϫ2.30 (m, 2 H, NϪCHϪCH), 2.32 (s, 3 H, CH3N) ppm. 13C
NMR (200 MHz, CDCl3): δ ϭ 25.0 (CH2ϪCH2ϪCHϪNH2), 25.2
Bourg, J-C. Broudic, O. Conocar, J. J. E. Moreau, D. Meyer,
[4e]
M. Wong Chi Man, Chem. Mater. 2001, 13, 491Ϫ499.
Sanchez, G. J. de A. A. Soler-Illia, F. Ribot, T. Lalot, C. R.
Mayer, V. Cabuil, Chem. Mater. 2001, 13, 3061Ϫ3083.
de A. A. Soler-Illia, C. Sanchez, B. Lebeau, J. Patarin, Chem.
C.
[4f]
G. J.
(CH2ϪCH2ϪCHϪNH),
30.4
(CH2ϪCHϪNH2),
33.5
(CH2ϪCHϪNHϪCH3), 36.1 (CH3ϪNH), 54.9 (CHϪNH2), 65.4
(CHϪNHϪCH3) ppm.
[4g]
Rev. 2002, 102, 4093Ϫ4138.
C. Sanchez, G. J. de A. A.
Soler-Illia, F. Ribot, D. Grosso, C. R. Chim. 2003, 6,
16c: Yield: 84%. 1H NMR (200 MHz, CDCl3): δ ϭ 2.23 (s, 3 H,
NHϪCH3), 3.41 (s, 2 H, C6H5ϪCH2), 7.20Ϫ7.32 (m, 5 H, C6H5)
ppm. 13C NMR (200 MHz, CDCl3): δ ϭ 43.4 (CH3ϪNH), 57.7
1131Ϫ1151.
[5] [5a]
J. J. E. Moreau, L. Vellutini, M. Wong Chi Man, C. Bied,
[5b]
J. Am. Chem. Soc. 2001, 123, 1509Ϫ1510.
C. Bied, J. J. E.
(C6H5ϪCH2ϪN), 126.7 (Caryl-H), 128.1 (Caryl-H), 140.3 (Caryl
)
Moreau, L. Vellutini, M. Wong Chi Man, J. Sol-Gel. Sci. Tech-
nol. 2003, 26, 583Ϫ586.
ppm.
16d: Yield: 63%. 1H NMR (200 MHz, CDCl3): δ ϭ 2.93 (s, 3 H,
NϪCH3), 7.14Ϫ7.19 (m, 3 H, C6H5), 7.25Ϫ7.36 (m, 2 H, C6H5)
ppm. 13C NMR (200 MHz, CDCl3): δ ϭ 37.8 (CH3ϪNH), 121.0
(Caryl-H), 128.1 (Caryl-H), 129.5 (Caryl-H), 138.6 (Caryl) ppm.
16e: Yield: 70%. 1H NMR (200 MHz, CDCl3): 1H NMR
(200 MHz, CDCl3): δ ϭ 2.34 (s, 3 H, CH3ϪN), 2.93 (d, 2 H,
C6H5ϪCH2), 3.43 (t, 1 H, CHϪN), 3.63 (s, 3 H, CH3ϪO),
7.17Ϫ7.25 (m, 5 H, C6H5) ppm. 13C NMR (200 MHz, CDCl3):
δ ϭ 34.7 (C6H5ϪCH2ϪN), 39.5 (CH3ϪN), 51.6 (CH3ϪO), 64.6
(CHϪN), 126.7 (Caryl-H), 128.5 (Caryl-H), 129.1 (Caryl-H), 137.1
(Caryl), 174.7 (CO) ppm. MS [FAB (ϩ)] m/z (%) ϭ 194 (100) [M ϩ
1]. C11H15NO2 (193.11): calcd. C 68.37, H 7.82, N 7.25; found C
69.02, H 7.93, N 7.47.
J. J. E Moreau, L. Vellutini, M. Wong Chi Man, C. Bied,
[6] [6a]
´
J.-L. Bantignies, P. Dieudonne, J.-L. Sauvajol, J. Am. Chem.
Soc. 2001, 123, 7957Ϫ7958.
M. Wong Chi Man, C. Bied, J.-L. Bantignies, P. Dieudonne, J.-
[6b]
J. J. E. Moreau, L. Vellutini,
´
L. Sauvajol, Mater. Res. Soc. Symp. Proc. 2002, 726, 235Ϫ242.
[6c]
J. J. E Moreau, L. Vellutini, M. Wong Chi Man, C. Bied,
[6d]
Chem. Eur. J. 2003, 9, 1594Ϫ1599.
Pichon, M. Wong Chi Man, C. Bied, H. Pritzkow, J.-L. Ban-
J. J. E Moreau, B. P.
´
tignies, P. Dieudonne, J.-L. Sauvajol, Angew. Chem. 2004, 116,
205Ϫ208; Angew. Chem. Int. Ed. 2004, 43, 203Ϫ206.
[7] [7a]
A. Adima, J. J. E. Moreau, M. Wong Chi Man, J. Mater.
[7b]
Chem. 1997, 7, 2331Ϫ2333.
Man, Coord. Chem. Rev. 1998, 178Ϫ180, 1073Ϫ1084.
Adima, J. J. E. Moreau, M. Wong Chi Man, Chirality 2000,
J. J. E. Moreau, M. Wong Chi
[7c]
A.
[7d]
12, 411Ϫ420.
C. Bied, D. Gauthier, J. J. E Moreau, M.
Wong Chi Man, J. Sol-Gel Sci. Technol. 2001, 20, 313Ϫ320. [7e]
A. Brethon, J. J. E. Moreau, M. Wong Chi Man, Tetrahedron:
Asymmetry 2004, 15, 495Ϫ502.
Preparation of 16b, 16d and 16e in One Step: The amine
(33.5 mmol)
and
(chloromethyl)trimethylsilane
(3.56 g,
16.75 mmol) were introduced into a glass tube. The tube was then
sealed under vacuum and placed in a drying oven at 87 °C with an
iron protection. After 18 hours the tube was taken out from the
oven and opened at room temperature. The residue was placed in
[8]
M. Fiorini, G. M. Giongo, J. Mol. Catal. 1979, 5, 303Ϫ308.
[9] [9a]
C. Eaborn, N. Retta, J. D. Smith, J. Chem. Soc., Dalton
Trans. 1983, 905Ϫ909. [9b] R. Brost, G. C. Bruce, S. L. Grundy,
S. R. Stobart, Inorg. Chem. 1993, 32, 5195Ϫ5200.
Eur. J. Org. Chem. 2004, 2582Ϫ2588
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2587

A. Adima, C. Bied, J. J. E. Moreau, M. Wong Chi Man
FULL PAPER
[10] [10a]
Y. Sato, H. Sakakibara, J. Organomet. Chem. 1979, 166,
295Ϫ296. [12f] M. D. M. Gray, D. J. H. Smith, Tetrahedron Lett.
1980, 21, 859Ϫ860. [12g] J. Zwierzak, J. Brylikowska-Piotriwicz,
[10b]
303Ϫ307.
45, 613Ϫ617.
Y. Sato, Y. Yargi, M. Koto, J. Org. Chem. 1980,
[10c]
M. Hori, Y. Sato, N. Shirai, F. Sumiya, J.
Angew. Chem. 1977, 89, 552Ϫ553; Angew. Chem. Int. Ed. Engl.
[12h]
Org. Chem. 1989, 54, 836Ϫ840.
1977, 16, 107Ϫ108.
T. Takata, A. Maturu, Tetrahedron
Lett. 1984, 34, 3631Ϫ3632. [12i] S. Padmanabhan, N. L. Reddy,
G. J. Durant, Synth. Commun. 1997, 27, 691Ϫ699.
N. Shirai, Y. Sato, J. Org. Chem. 1988, 53, 194Ϫ196.
T. Tanaka, N. Shirai, Y. Sato, Chem. Pharm. Bull. 1992, 40,
[11] [11a] R. Tacke, J. Becht, O. Dannapel, R. Ahlrichs, U. Schneider,
W. S. Sheldrick, J. Hahn, F. Kiesgen, Organometallics 1996,
[13] [13a]
[13b]
[11b]
15, 2060Ϫ2077.
R. Tacke, B. Ulmer, B. Wagner, M. Arlt,
Organometallics 2000, 19, 5297Ϫ5309. [11c] A. R. Bassindale, Y.
I. Baukov, P. G. Taylor, V. V. Negrebetsky, J. Organomet. Chem.
2002, 655, 1Ϫ6.
518Ϫ520.
[14]
J. F. Larrow, E. N. Jacobsen, J. Org. Chem. 1994, 59,
1939Ϫ1942.
[12] [12a] S. Krishnamurthy, Tetrahedron. Lett. 1982, 23, 3315Ϫ3318.
J. E. Noll, J. L. Speier, B. F. Daubert, J. Am. Chem. Soc.
[15] [15a]
[15b]
[12b] R. Grigg, T. R. B. Mitchell, J. Chem. Soc., Chem. Commun.
1951, 73, 3867Ϫ3871.
J. L. Speier, C. A. Roth, J. W. Ryan,
[12c]
[15c]
1981, 611Ϫ612.
S. B. Kadin, J. Org. Chem. 1973, 38,
J. Org. Chem. 1971, 36, 120Ϫ126.
D. Brondani, R. J. P.
[12d]
1348Ϫ1350.
M. Selva, A. Bomben, P. Tundo, J. Chem.
Corriu, S. El Ayoubi, J. J. E. Moreau, M. Wong Chi Man,
Tetrahedron Lett. 1993, 34, 2111Ϫ2114.
Received February 6, 2004
Soc., Perkin Trans. 1 1997, 1, 1041Ϫ1045. [12e] E. M. Briggs, G.
W. Brown, J. Jiricny, M. F. Meidine, Synth. Commun. 1980,
2588
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 2582Ϫ2588