Synthesis and structure of potentially biologically active N-(silylmethyl)tetrahydropyrimidin-2-ones

Article abstract of DOI:10.1007/s11172-014-0705-5

A transsilylation of 1,3-bis(trimethylsilyl)tetrahydropyrimidin-2-one with (chloromethyl)-chlorosilanes ClCH₂SiMenCl_3-n (n = 0, 2) gave the corresponding 1,3-bis[(chlorosilyl)-methyl]tetrahydropyrimidin-2-ones. New Si-containing tetrahydropyrimidin-2-ones were synthesized by the exchange reactions at the Si - Cl and Si - N bonds of these compounds. The structures of all the synthesized compounds were confirmed by multinuclear NMR spectroscopy. Virtual screening using the PASS program showed that these compounds can exhibit certain types of biological activity with 40 - 94% probability.

Full text of DOI:10.1007/s11172-014-0705-5

Russian Chemical Bulletin, International Edition, Vol. 63, No. 9, pp. 2081—2086, September, 2014
2081
Synthesis and structure of potentially biologically active
Nꢀ(silylmethyl)tetrahydropyrimidinꢀ2ꢀones
N. F. Lazareva and I. M. Lazarev
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
1 ul. Favorskogo, 664033 Irkutsk, Russian Federation.
Eꢀmail: nataly_lazareva@irioch.irk.ru
A transsilylation of 1,3ꢀbis(trimethylsilyl)tetrahydropyrimidinꢀ2ꢀone with (chloromethyl)ꢀ
chlorosilanes ClCH2SiMenCl3–n (n = 0, 2) gave the corresponding 1,3ꢀbis[(chlorosilyl)ꢀ
methyl]tetrahydropyrimidinꢀ2ꢀones. New Siꢀcontaining tetrahydropyrimidinꢀ2ꢀones were synꢀ
thesized by the exchange reactions at the Si—Cl and Si—N bonds of these compounds. The
structures of all the synthesized compounds were confirmed by multinuclear NMR spectroꢀ
scopy. Virtual screening using the PASS program showed that these compounds can exhibit
certain types of biological activity with 40—94% probability.
Key words: 1,3ꢀbis(trimethylsilyl)tetrahydropyrimidinꢀ2ꢀone, 1,3ꢀbis(silylmethyl)tetraꢀ
hydropyrimidinꢀ2ꢀones, transsilylation, transetherification, potential biological activity.
In the last decades, chemistry of urea derivatives is
under rapid development.1 Derivatives of cyclic urea are
of special interest as building blocks in synthetic organic
chemistry,2—5 unique organic ligands,6—9 solvents and coꢀ
solvents.10,11 These compounds exhibit considerable antiꢀ
bacterial,12,13 sedativeꢀhypnotic,14,15 antitumor,16,17 and
antiviral18 activity. It should be noted that derivatives of
cyclic ureas are active inhibitors of enzymes: ꢀsecretase
(BASE1)19,20 and HIVꢀ1 protease.21—29 Compounds inꢀ
hibiting synthesis of BASE1 can be used for treatment of
Alzheimer disease. Lopinavir (ABTꢀ378) is one of the main
components of highly efficient agent Kaletra used in the
therapy of HIVꢀinfected patients.30,31 Its molecule conꢀ
tains a structural fragment of cyclic urea, viz., tetrahydroꢀ
pyrimidinꢀ2ꢀone. It should be noted that a number of lopiꢀ
navir analogues were also synthesized, in which the tetraꢀ
hydropyrimidinꢀ2ꢀone moiety is replaced with other
heterocyclic fragments.32,33 It turned out that in this seꢀ
ries lopinavir has the best inhibiting activity against HIVꢀ1
protease and pharmacokinetic profile.
meability improves, the agents remain active for a longer
time. Recently, the data on the formation of silicon hyperꢀ
valent complexes by siderophores E. coli under physiologꢀ
ical conditions were obtained.37,38 These results open very
interesting aspects of silicon chemistry concerning the role
of hypervalent silicon compounds in biochemical processes
in vivo. The following data on biological activity of
Nꢀsilylmethylated ureas are known: they exhibit antitumor
activity,39,40 regulate lipid metabolism,41 inhibit proteꢀ
ases,42 and are used in dermatology.43
Taking into account all the said above, we expect that
introduction of siliconꢀcontaining groups in the molecules
of cyclic ureas can lead to the preparation of compounds
possessing biological activity. The purpose of the present
work is the development of methods for the synthesis of
Nꢀ(silylmethyl)ꢀsubstituted tetrahydropyrimidinꢀ3ꢀones,
studies of their structures and chemical properties.
Results and Discussion
The interest to the study of biological activity of siliꢀ
conꢀcontaining compounds came into being in the middle
of last century34,35 and these studies successfully continue
at the present time.36 Unlike carbon, silicon atom has
considerably lower electronegativity and larger covalent
radius and contains vacant 3d orbitals. Modification of
organic compounds via introduction in their molecules
of Siꢀcontaining groups leads to the change in stereoꢀ
electronic structure and, as a consequence, to the change
in pharmacological properties of compound: the solubility
of medicines in lipids increases, their cell membrane perꢀ
There are two main approaches to the synthesis of
Nꢀ(silylmethyl)ꢀsubstituted tetrahydropyrimidinꢀ2ꢀones:
(1) cyclization of Nꢀsilylmethylated 1,3ꢀdiaminopropanes
and (2) substitution reactions at the nitrogen atom of tetraꢀ
hydropyrimidinꢀ2ꢀone. We used the first method earlier44
on a model cyclization reaction of N,N´ꢀbis(silylmethyl)ꢀ
propylenediamines (EtO)3–nMenSiCH2N(CH2)3NCH2ꢀ
SiMen(OEt)3–n (n = 0, 2) to synthesize 1,3ꢀbis(silylꢀ
methyl)tetrahydropyrimidinꢀ2ꢀones, which reacted with
BCl3 to give the corresponding chlorosilanes (Scheme 1).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2081—2086, September, 2014.
1066ꢀ5285/14/6309ꢀ2081 © 2014 Springer Science+Business Media, Inc.

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Lazareva and Lazarev
Scheme 1
The second method is the reaction of halomethylsiꢀ
lanes HalCH2SiX3 with preliminary metallated or silylatꢀ
ed ureide nitrogen atom. The transsilylation of carboxylic
acid Nꢀtrimethylsilylamides with chloromethylsilanes
ClCH2SiMenCl3–n (n = 0—2) leads to carboxylic acid
Nꢀ(silylmethyl)amides under mild conditions in good
yields.45 As a rule, the silicon atom in these compounds is
pentacoordinated. Exchange reactions involving labile
Si—Cl bonds can lead to a number of carboxylic acid
Nꢀ(silylmethyl)amides with a broad range of substituents
at the silicon atom. We showed that 1,3ꢀbis(triꢀ
methylsilyl)tetrahydropyrimidinꢀ2ꢀone (1) reacts with
ClCH2SiMe2Cl (the ratio of reagents 1 : 1) in heptane with
the formation of 1ꢀ[(chlorodimethyl)silylmethyl]ꢀ3ꢀtriꢀ
methylsilyltetrahydropyrimidinꢀ2ꢀone (2) in high yield as
the only transsilylation product.46 In continuation of these
findings, we studied the reaction of compound 1 with
ClCH2SiMe2Cl in the ratio of 1 : 2 (Scheme 2). The subꢀ
stitution of the second trimethylsilyl group takes place
under more drastic conditions, the reaction reached comꢀ
pletion upon heating the mixture for several hours without
solvent and leads to the formation of 1,3ꢀbis[(chloroꢀ
dimethylsilyl)methyl]tetrahydropyrimidinꢀ2ꢀone (3). This
method gave compound 3 in higher yield than that in
the exchange reaction44 (69% and 49%, respectively).
The transsilylation of compound 1 with two moles of
ClCH2SiMe2Cl at room temperature in heptane or chloroꢀ
form comes to completion only after several days. The
product of Nꢀtranssilylation of trimethylsilyl group in urea 2.
In the 29Si NMR spectra, the intermediate A is representꢀ
ed by the signals at  10.01 and —41.28 (Me2Si* and Me2Si
groups, respectively). This process is slower than Nꢀtransꢀ
silylation of 1 and reaches completion after 10 h, which is
indicated by the gradual decrease in the intensities of sigꢀ
nals for the Me3SiN groups in the H NMR spectra of
compound 2. The intermediate A completely rearranges
into the final product 3 only within 2 days.
1
Scheme 2
1
studies of this process in CDCl3 using H NMR spectroꢀ
Reagents and conditions: i. ClCH2SiMe2Cl, CDCl3;
ii. ClCH2SiMe2Cl.
scopy at room temperature showed that this is a twoꢀstep
reaction (see Scheme 2). The first step gives the transsilylꢀ
ation product at one trimethylsilyl group of compound 1
to form urea 2 with the pentacoordinated silicon atom.
This is indicated by the gradual decrease in the intensity of
the signal for the Me3Si group ( = 0.24) in the 1H NMR
spectra of compound 1 and appearance of new signals
at  0.27 and 0.60 (Me3Si and Me2Si groups, respectively)
belonging to compound 2. In the 29Si NMR spectra, new
signals attributable to these groups are observed at  14.73
and –41.63. Simultaneously, already ~45 min after the
Urea 1 reacts with (chloromethyl)trichlorosilane
ClCH2SiCl3 (the ratio of reagents 1 : 2) in thoroughly dried
hexane, forming 1,3ꢀbis[(trichlorosilyl)methyl]tetrahydroꢀ
pyrimidinꢀ2ꢀone (4) in high yield (Scheme 3). The prodꢀ
uct is a fine white powder, extremely sensitive to the
air moisture: the powder deliquesces in air already after
several minutes. According to NMR spectroscopy,
compound 4 contains only insignificant amount of impuꢀ
rities (no more than 3—5%). The spectral characteristics
do not change for several days if the sample is stored in
a sealed evacuated tube at –78 C. Unfortunately, any
attempts to obtain a pure sample by recrystallization failed,
these manipulations led only to the appearance of addiꢀ
1
moment of mixing reagents, the H NMR spectrum exꢀ
hibits weak, but gradually growing signals at  0.38
(Me2Si*), 2.97 (SiCH2), and 3.27 (NCH2) belonging to
compound A (see Scheme 2). The intermediate A is the

Nꢀ(Silylmethyl)tetrahydropyrimidinꢀ2ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2083
Scheme 3
Scheme 4
tional signals in the NMR spectra, some of which can be
assigned to the hydrolysis products. Compound 4 decomꢀ
poses upon heating and prolonged storage at room temꢀ
perature even in a sealed tube.
Treatment of compound 4 with thoroughly dried methꢀ
anol in the presence of triethylamine in pentane leads to
the formation of 1,3ꢀbis[(trimethoxysilyl)methyl]tetraꢀ
hydropyrimidinꢀ2ꢀone (5) in 78% yield. The reaction was
carried out with vigorous stirring at 0 5 C, raising the
reaction temperature above 10 C leads to a sharp deꢀ
crease in the yield of compound 5 (down to 30%). Urea 5
was also synthesized by an alternative method in satisꢀ
factory yield (51%) by the reaction of (chloromethyl)ꢀ
trimethoxysilane with compound 1 (see Scheme 3). This
reaction requires heating of the mixture of reagents in the
ratio of 1 : 2 in xylene in the presence of a catalytic amount
of anhydrous AlCl3, simultaneously distilling off chloroꢀ
trimethylsilane. Despite the fact that chlorotrimethylsilane
in this reaction was isolated in almost quantitative yield,
the yield of compound 5 was only 51% because of formaꢀ
tion of considerable amounts of unidentified polymeric
products. The corresponding 1,3ꢀbis(silatranylmethyl)ꢀ
tetrahydropyrimidinꢀ2ꢀone (6) was synthesized by transꢀ
etherification of compound 5 with triethanolamine.
Compound 3 smoothly reacts with MeMgI in diethyl
ether or tetrahydrofuran with the formation of the correꢀ
sponding 1,3ꢀbis[(trimethylsilyl)methyl]tetrahydropyrꢀ
imidinꢀ2ꢀone (7) (Scheme 4), with the carbonyl group
remaining intact under these conditions.
Scheme 5
silicon atom in the 29Si NMR spectra of compound 3 was
found in considerably more lowꢀfield region as compared
to that for compound 2 existing as a (O—Si)ꢀchelate with
a pentacoordinated silicon atom46 ( –6.65 and –41.63,
respectively). This can be caused by a competitive interacꢀ
tion of two silyl groups with the carbonyl group C=O well
known as a "flip—flop" rearrangement.47,48 The involveꢀ
ment of the carbonyl group in the C=OSi coordinative
binding is indicated by the downfield displacement of its
chemical shift in the 13C NMR spectra as compared to
that in the structurally close urea 7, in which such an
interaction is absent ( 157.96 and 155.96, respectively).
1ꢀBenzylꢀ3ꢀ[(chlorodimethylsilyl)methyl]tetrahydropyrꢀ
imidinꢀ2ꢀone (8) is a bright representative of (O—Si)ꢀ
chelates. The pentacoordination of the silicon atom in
compound 8 is indicated by a considerable upfield disꢀ
placement of its chemical shift in the 29Si NMR spectra,
The reaction of compound 2 with benzyl chloride gives
1ꢀbenzylꢀ3ꢀ[(chlorodimethylsilyl)methyl]tetrahydropyrꢀ
imidinꢀ2ꢀone (8) (Scheme 5).
The structures of all the Nꢀsilylmethylated cyclic ureas
were confirmed by multinuclear NMR spectroscopy. Some
specific features of these structures should be highlighted.
Thus, according to the 29Si NMR spectra the two silicon
atoms in compound 3 are equivalent. The signal for the

2084
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
Lazareva and Lazarev
(400.1 (1H), 100.6 (13C), 79.5 (29Si) MHz) in CDCl3 using Me4Si
or cyclohexane as internal standards. Tetrahydropyrimidinꢀ2ꢀ
one was commercially available from Aldrich and used without
additional purification. 1,3ꢀBis(trimethylsilyl)tetrahydropyrꢀ
imidinꢀ2ꢀone (1) and 1ꢀ[(chlorodimethylsilyl)methyl]ꢀ3ꢀtriꢀ
methylsilyltetrahydropyrimidinꢀ2ꢀone (2) were synthesized acꢀ
cording to the procedure described by us earlier.46 Silanes were
distilled immediately before use with addition of 3—5% of Bu3N
to bind HCl. Solvents were purified according to the known
procedures.54 Syntheses which used hydrolytically unstable comꢀ
pounds were carried out in the Schlenk glassware under dry argon.
1,3ꢀBis[(chlorodimethylsilyl)methyl]tetrahydropyrimidinꢀ2ꢀ
one (3). An excess of (chloromethyl)chlorodimethylsilane (15 mL,
0.11 mol) was added dropwise to compound 1 (7.4 g, 0.03 mol)
with vigorous stirring. After an exothermic reaction ceased, the
mixture was refluxed for 3 h with a reflux condenser. Then,
Me3SiCl was evaporated from the reaction mixture, the residue
was distilled in vacuo to give compound 3 (6.5 g, 69%), b.p.
203—205 C (1.5 Torr), nD20 1.4712. 1H NMR, : 0.57 (s, 12 H,
Me2Si); 2.08 (m, 2 H, CCH2C); 2.90 (s, 4 H, NCH2Si); 3.38
(m, 4 H, NCH2C). 13C NMR, : 4.94 (Me2Si); 21.07 (CCH2C);
43.24 (NCH2C); 47.02 (NCH2Si); 157.96 (C=O). 29Si NMR,
: –6.65 (25 C). Found (%): C, 38.36; H, 6.93; N, 8.97; Si, 17.70;
Cl, 22.26. C10H22Cl2N2OSi2. Calculated (%): C, 38.33; H, 7.08;
N, 8.94; Si, 17.92; Cl, 22.63.
1,3ꢀBis([trichlorosilylmethyl)tetrahydropyrimidinꢀ2ꢀone (4).
A solution of (chloromethyl)trichlorosilane (3.66 g, 0.02 mol) in
hexane (15 mL) was added dropwise (slowly, over ~3 h) to a soluꢀ
tion of (compound 1 (2.44 g, 0.01 mol) in hexane (50 mL) under
dry argon with vigorous stirring. After 24 h, a precipitate formed
was filtered off under argon using reverse filtration, washed with
dry pentane, and dried in vacuo. The yield was 3.8 g (96%).
1H NMR, : 1.99 (m, 2 H, CCH2C); 2.96 (s, 4 H, NCH2Si);
3.39 (m, 4 H, NCH2C). 13C NMR, : 21.07 (CCH2C); 45.15
(NCH2C); 45.99 (NCH2Si); 159.82 (C=O). 29Si NMR, : –13.08.
Found (%): C, 18.65; H, 2.71; N, 7.21. C6H10Cl6N2OSi2. Calꢀ
culated (%): C, 18.24; H, 2.55; N, 7.09.
1
which is close to that in compound 2. In the H NMR
spectrum of urea 6, the protons of the NCH2 and OCH2
groups of the silatrane framework resonate as two triplets
( 2.79 and 3.72, respectively) in the region indicative for
silatranes.49 The pentacoordination of the silicon atom in
compound 6 is indicated by the upfield shift of its signal in
the 29Si NMR spectrum as compared to that in the model
compound 5 (–79.96 and –56.85, respectively).
In the search for possible practical application of the
synthesized compounds, we carried out their virtual screenꢀ
ing using the PASS program50 developed in the V. N.
Orekhovich Research Institute of Biomedical Chemistry
of the Russian Academy of Medical Sciences and successꢀ
fully used for the prediction of biological activity of new
compounds.51—53 Based on the structural formula of comꢀ
pound, this program predicts more than 500 kinds of bioꢀ
logical activity and helps to determine the scope of experꢀ
imental screening when looking for compounds with useꢀ
ful properties. All the synthesized compounds were preꢀ
dicted to have various kinds of biological activity with
more than 50% probability. It should be noted that a real
screening for biological activity could have been done for
only compounds 5—7, since compounds with the labile
Si—Cl bond are not suitable for this purpose. According to
the virtual screening data, compound 5 can potentially
possess inhibiting activity against a number of enzymes
(with 53—73% probability), stimulation of leukopoesis
(with 52% probability), stimulation of kidney function
(with 63% probability); for compound 6 — antitumor acꢀ
tivity (with 78% probability), inhibitory activity against
a number of enzymes (with 40—59% probability), stimulaꢀ
tion of kidney function (with 52% probability), analeptic
activity (with 41—46% probability). Compound 7 can regꢀ
ulate metabolism (with 94% probability), exhibit antidiaꢀ
betic effect (with 84% probability), antiviral activity against
HIV (with 81% probability), general antiviral activity (with
77% probability), antispasmodic properties (with 60%
probability). These data show that experimental biologiꢀ
cal testing of ureas 5—7 can give interesting results.
1,3ꢀBis[(trimethoxysilyl)methyl]tetrahydropyrimidinꢀ2ꢀone
(5). A. A mixture of urea 1 (24.4 g, 0.1 mol) and chloroꢀ
methyl(trimethoxy)silane (34 g, 0.2 mol) was heated in the presꢀ
ence of catalytic amount of anhydrous AlCl3 (~0.1 g) with simulꢀ
taneous distillation of Me3SiCl. The residue was distilled in vacuo,
the yield was 18.7 g (51%), b.p.. 221—226 C (1 Torr).
B. Compound 4 (3.95 g, 0.01 mol) was carefully added with
vigorous stirring to a solution of anhydrous methanol (3.2 g,
0.1 mol) and triethylamine (15 mL, 0.1 mol) in dry pentane
(150 mL) cooled to 0 C, the temperature of the reaction mixture
was maintained within 0 5 C. Then, the temperature was slowꢀ
ly raised to ambient and the reaction mixture was stirred at room
temperature for 10 h and then allowed to stand for 18 h.
A precipitate of triethylamine hydrochloride was filtered off and
washed with pentane (2×30 mL). Pentane was evaporated
in vacuo, the residue was distilled in vacuo to obtain compound 5
(2.8 g, 78%), b.p. 220—223 C (1 Torr). 1H NMR, : 1.95 (m, 2 H,
CCH2C); 2.88 (s, 4 H, NCH2Si); 3.30 (m, 4 H, NCH2C); 3.57
(s, 18 H, SiOMe). 13C NMR, : 21.07 (CCH2C); 39.73 (NCH2C);
47.89 (NCH2Si); 56.45 (SiOMe); 156.56 (C=O). 29Si NMR,
: –56.85. Found (%): C, 39.33; H, 7.89; N, 7.87. C12H28N2O7Si2.
Calculated (%): C, 39.11; H, 7.66; N, 7.60.
In conclusion, in the present work we have shown that
the transsilylation of 1,3ꢀbis(trimethylsilyl)tetrahydropyrꢀ
imidinꢀ2ꢀone with silanes ClCH2SiMenCl3–n (n = 0—2)
can be successfully used not only for the formation of one
C(O)N—C—Si fragment in ureas, but also in the preparaꢀ
tion of 1,3ꢀbis(silylmethyl)tetrahydropyrimidinꢀ2ꢀones.
New 1ꢀorganylꢀ3ꢀ(silylmethyl)ꢀ and 1,3ꢀbis(silylmethyl)ꢀ
tetrahydropyrimidinꢀ2ꢀones were synthesized by the exꢀ
change reactions of the Si—Cl and N—SiMe3 bonds. Virꢀ
tual screening using the PASS program showed that the
synthesized compounds can potentially exhibit various
kinds of biological activity with high probability.
Experimental
1,3ꢀBis(silatranylmethyl)tetrahydropyrimidinꢀ2ꢀone (6). One
drop of a 10% solution of MeONa in methanol was added to
a mixture of compound 5 (3.68 g, 0.01 mol) and triethanolamine
NMR spectra of 10—20% solutions of compounds were reꢀ
corded on JEOLꢀ90Q and Bruker DPXꢀ400 spectrometers

Nꢀ(Silylmethyl)tetrahydropyrimidinꢀ2ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2085
(2.98 g, 0.02 mol), the mixture was vigorously stirred until comꢀ
plete homogenization (10 min). Methanol was removed in vacuo,
the residue was recrystallized from benzene. The yield was 2.97 g
(63%). 1H NMR, : 1.82 (m, 2 H, CCH2C); 2.73 (s, 4 H,
NCH2Si); 2.79 (t, 12 H, NCH2CH2O, 3J = 5.9 Hz); 3.27 (m, 4 H,
NCH2C); 3.72 (t, 12 H, NCH2CH2O, 3J = 5.9 Hz). 13C NMR,
: 22.45 (CCH2C); 38.31 (NCH2C); 47.20 (NCH2Si); 50.78
(NCH2CH2O); 57.63 (NCH2CH2O); 157.23 (C=O). 29Si NMR,
: –79.96. Found (%): C, 45.71; H, 7.42; N, 11.71. C18H34N4O7Si2.
Calculated (%): C, 45.55; H, 7.22; N, 11.80.
1,3ꢀBis[(trimethylsilyl)methyl]tetrahydropyrimidinꢀ2ꢀone (7).
Urea 3 (6 g, 0.02 mol) was slowly added to a solution of freshly
prepared methylmagnesium bromide (0.06 mol) in diethyl ether
with stirring, maintaining the temperature of the reaction mixꢀ
ture at ~5 C. Then, the mixture was stirred for 10 h at room
temperature. The ethereal solution was decanted, a precipitate was
washed with diethyl ether, the organic solutions were combined.
The solvent was evaporated in vacuo, the residue was distilled
in vacuo to obtain compound 7 (4.2 g, 78%), b.p. 135—137 C
(1.5 Torr), nD20 1.4497. 1H NMR, : 0.06 (s, 18 H, Me3Si); 1.92
(m, 2 H, CCH2C); 2.85 (s, 4 H, NCH2Si); 3.22 (m, 4 H,
NCH2C). 13C NMR, : –1.49 (Me3Si); 22.61 (CCH2C); 39.78
(NCH2C); 48.45 (NCH2Si); 155.96 (C=O). 29Si NMR, : –1.05.
Found (%): C, 52.61; H, 10.19; N, 10.37. C12H28N2OSi2. Calꢀ
culated (%): C, 52.88; H, 10.36; N, 10.28.
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1ꢀBenzylꢀ3ꢀ[(chlorodimethylsilyl)methyl]tetrahydropyrimidꢀ
inꢀ2ꢀone (8). A mixture of compound 2 (2.78 g, 0.01 mol) and
benzyl chloride (1.5 g, 0.012 mol) was refluxed for 1 h, then,
chlorotrimethylsilane was distilled off. Compound 8 (1.86 g, 63%)
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was isolated by distillation in vacuo, b.p. 230—232

C (1 Torr),
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a dense pale yellow liquid with a weak specific odor of benzyl
1
chloride, slowly crystallizes in bulk. H NMR, : 0.65 (s, 6 H,
Me2Si); 1.97 (m, 2 H, CCH2C); 2.88 (s, 4 H, NCH2Si); 3.32
(t, 4 H, NCH2C, 3J = 6.10 Hz); 4.47 (s, 2 H, PhCH2); 7.29 (5 H,
Ph). 13C NMR, : 7.41 (Me2Si); 20.81 (CCH2C); 45.59 (NCH2Si);
43.70; 44.42 (NCH2C); 51.96 (PhCH2); 127.85, 128.76, 128.34,
136.04 (Ph); 158.03 (C=O). 29Si NMR, : –41.76. Found (%):
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Received April 25, 2014;
in revised form June 4, 2014