Chemoselective reactions of trimethylsilylpropynal with aminopyrimidines and amino acid esters

Article abstract of DOI:10.1134/S1070428011100174

Highly efficient chemoselective 1,2-addition of 2-aminopyrimidines and D,L-amino acid esters to substituted propynals was performed. Acid-catalyzed addition of 2-aminopyrimidine and 2-amino-4-methylpyrimidine to trimethylsilyl- and phenylpropynals gave pr

Full text of DOI:10.1134/S1070428011100174

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 10, pp. 1544–1550. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.V. Mareev, E.Yu. Mareeva, M.V. Andreev, S.S. Gulyaev, I.V. Mitroshina, A.S. Medvedeva, 2011, published in Zhurnal
Organicheskoi Khimii, 2011, Vol. 47, No. 10, pp. 1516–1522.
Chemoselective Reactions of Trimethylsilylpropynal
with Aminopyrimidines and Amino Acid Esters
A. V. Mareev, E. Yu. Mareeva, M. V. Andreev, S. S. Gulyaev,
I. V. Mitroshina, and A. S. Medvedeva
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: amedved@irioch.irk.ru
Received February 10, 2011
Abstract—Highly efficient chemoselective 1,2-addition of 2-aminopyrimidines and D,L-amino acid esters to
substituted propynals was performed. Acid-catalyzed addition of 2-aminopyrimidine and 2-amino-4-methyl-
pyrimidine to trimethylsilyl- and phenylpropynals gave previously unknown acetylenic aminals. Reactions of
α-amino acid methyl esters (alanine and lysine) with trimethylsilylpropynal led to the formation of new aza
enynes in high yield. Regardless of the reactant ratio, trimethylsilylpropynal reacted with lysine at both amino
groups with formation of bis-aza enyne.
DOI: 10.1134/S1070428011100174
Propynals occupy an important place among acety-
lene derivatives. They are ambident bielectrophiles and
are used as building blocks in fine organic synthesis
and total syntheses of highly effective antibiotics of
natural origin, as well as in the design of promising
materials possessing magnetic or electrooptical prop-
erties [1]. Heteroatom-containing propynals attract
specific attention in the chemistry of α,β-acetylenic
aldehydes. The presence of a silicon or germanium
atom at the triple bond stabilizes propynal molecule
and adducts derived therefrom, whereas subsequent
demetalation under mild conditions could produce ana-
logs with terminal triple bond. We previously showed
that silicon- and germanium-containing propynals and
their carbon analog react with primary amines in the
absence of a catalyst chemoselectively at the aldehyde
group with formation of the corresponding Schiff
bases [2].
on the conditions [3]. It was also found that reactions
of heteroelement-containing propynals with nitrogen-
centered 1,3-binucleophiles can involve one or two
reaction centers in the propynal and binucleophile.
2-Aminopyridine reacted with trimethylsilyl(or tri-
ethylgermyl)propynal generated in situ under condi-
tions of tandem oxidation–amination of the corre-
sponding alcohols by the action of MnO2–SiO2 under
microwave (MW) irradiation to produce imidazo-
[1,2-a]pyridine-3-carbaldehyde [4]. Cascade assembly
of the product involved the triple bond in the propynal
and both nucleophilic centers in 2-aminopyridine.
Acid-catalyzed reaction of trimethylsilylpropynal
with 2-aminopyridine followed previously unknown
scheme with formation of N-(pyridin-2-yl)-2-(trimeth-
ylsilylethynyl)-1,2-dihydropyridine-3,5-dicarbalde-
hyde in high yield. Both reaction center in the propynal
molecule participated in this process, and the resulting
heterocycle was built of three aldehyde molecules and
one amine molecule [5]. Analogous reaction of phenyl-
propynal with 2-aminopyridine resulted in self-as-
sembly of hitherto unknown 3-[pyridin-2-ylamino-
(phenyl)methyl]imidazo[1,2-a]pyridine from two
amine molecules and one molecule of the aldehyde [6].
In both cases, the cascade processes involved two
electrophilic centers in the propynal molecule. The
reactions of trimethylsilyl- and triethylgermylpropinals
However, the nature of primary amine and reaction
conditions could affect to a considerable extend both
chemoselectivity of the addition reaction and structure
of the products. For example, the addition of 2-amino-
ethanethiol to trimethylsilyl(or triethylgermyl)propynal
occurs chemoselectively at the carbonyl group with
formation of the corresponding Schiff bases or their
cyclization products, 2-[3-trimethylsilyl(or triethyl-
germyl)prop-2-yn-1-yl]-1,3-thiazolidines, depending
1544

CHEMOSELECTIVE REACTIONS OF TRIMETHYLSILYLPROPYNAL
1545
Scheme 1.
N
Me3Si
CHO +
R
N
NH2
Ia
IIa, IIb
Me3Si
R
CHO
N
SiMe3
Ia
N
N
CHO
CHO
R
N
N
H
N
III
t-BuOH–H2O, HCl (5 mol %)
25°C, 7 days
or MW (700 W), 18 min
SiMe3
IIa, IIb
N
N
SiMe3
R
N
N
N
H
N
R
H
IVa, IVb
N
R
N
N
OH
N
H
R
N
N
–H2O
SiMe3
V
R = H (a), Me (b).
with another nitrogenous 1,3-binucleophile, 1,2,4-tri-
azole-3-amine, in the absence of a catalyst chemo-
selectively occurred at the aldehyde group to produce
the corresponding aldehyde imines [3]. The above data
indicate that the reaction direction strongly depends on
the reactant nature and conditions.
The goal of the present work was to elucidate how
the nature of substituent at the triple bond in propynal
and the nature of primary amine affect chemoselec-
tivity of the addition of 2-aminopyrimidines (as nitro-
gen-centered 1,3-binucleophiles) and α-amino acid
methyl esters to trimethylsilyl- and phenylpropynals
and the structure of the final products.
We found that the nature of 1,3-binucleophile is the
determining factor. 2-Aminopyrimidine (IIa) and
2-amino-4-methylpyrimidine (IIb) reacted with tri-
methylsilylpropynal (Ia) and phenylpropynal (Ib)
chemoselectively at the carbonyl group with formation
of the corresponding acetylenic aminals IVa and IVb.
The reactions of trimethylsilylpropynal (Ia) with
aminopyrimidines IIa and IIb were carried out in
aqueous tert-butyl or isopropyl alcohol under acid
catalysis (5 mol % of HCl) at room temperature
(7 days) or under microwave irradiation (700 W,
18 min), and previously unknown aminals IVa and
IVb were formed in high yield (70–82%) instead of
expected 1,2-dihydropyridines III (Scheme 1). Ac-
cording to the NMR data, the reaction mixtures con-
tained no Schiff bases V. Likewise, chemoselective ad-
dition of 2-aminopyrimidine (IIa) at the aldehyde
group of phenylpropynal (Ib) afforded aminal IVc in-
stead of expected imidazopyridine VI [6] (Scheme 2).
The structure of the newly synthesized compounds
was confirmed by their elemental analyses and IR,
1
13
Raman, and H and C NMR spectra. The IR spectra
of IVa and IVb characteristically contained absorption
bands due to stretching vibrations of the triple C≡C
bond at 2165 and 2170 cm–1; vibrations of the Me3Si
group gave rise to absorption bands in the regions
1220–1250 and 815–840 cm–1. Bands in the region
1500–1585 cm–1 were assigned to stretching vibrations
of the pyrimidine ring (νC=C, νC=N) and δNH, while νNH
bands were observed at 3220–3410 cm–1. No νC≡C band
was observed in the IR spectrum of 3-phenyl-N,N′-bis-
(pyrimidin-2-yl)prop-2-yne-1,1-diamine (IVc), and the
presence of a triple bond in its molecule was con-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

MAREEV et al.
1546
Scheme 2.
N
Ph
CHO
+
N
NH2
Ib
IIa
Ph
N
N
N
N
Ph
IIa
N
NH
N
CHO
N
N
H
VI
Ph
t-BuOH–H2O, HCl (5 mol %)
25°C, 7 days
or MW (700 W), 18 min
IIa
N
N
Ph
N
N
N
N
H
H
IVc, 80%
N
N
N
H
OH
N
N
N
–H2O
Ph
VII
firmed by the Raman spectrum (ν 2236 cm–1). Presum-
ably, the reason is that molecule IVc possesses
a pseudosymmetry center, which makes stretching vi-
brations of the triple bond inactive in the IR spectrum.
ification and multidentate ligands for metal complex
catalysis [8, 9]. Taking into account that 2-aminopy-
rimidines are structural fragments of DNA and RNA
bases, their derivatives are promising from the view-
point of biological activity [10]. Comparison of the
behavior of 2-aminopyridines and 2-aminopyrimidines
IIa and IIb in acid-catalyzed reaction with propynal Ia
demonstrates that the nature of 1,3-binucleophile is the
main factor determining chemoselectivity of nucleo-
philic attack and reaction direction.
The different behavior of 2-aminopyrimidines IIa
and IIb as compared to 2-aminopyridine is likely to be
determined by their lower basicity (and hence nucleo-
philicity) [7], which does not favor heterocyclization
with participation of the triple bond. Selective forma-
tion of aminals IVa–IVc is also favored by their crys-
tallization from the reaction mixture. Compounds IVa–
IVc attract interest as substrates for subsequent mod-
Only a few data are available on functionalization
of esters of natural α-amino acids via reactions with
Scheme 3.
R
O
Et3N, PhH, 25°C, 1.5 h
MgSO4
OMe
O
Me
N
RCHO
+
OMe
NH2 ·HCl
Me
Ia, Ic
IXa
Xa, Xb, 62–69%
R
OMe
O
O
Et3N (2 equiv), PhH
25°C, 4 h, MgSO4
R
N
H2N
RCHO
+
OMe
N
·2HCl
IXb
NH2
Ia, Ic
XIa, XIb, 57–83%
Ia, Xa, XIa, R = Me3SiC≡C; Ic, Xb, XIb, R = Ph.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

CHEMOSELECTIVE REACTIONS OF TRIMETHYLSILYLPROPYNAL
1547
α,β-acetylenic aldehydes and ketones. Loh et al. [11]
reported on a one-step indium-catalyzed procedure for
the synthesis of N-allylprop-2-yn-1-amine from tri-
methylsilylpropynal, L-valine methyl ester, and allyl
bromide [11], and Crisp and Millan [12] described
formation of enaminones as a result of conjugate ad-
dition of the side-chain ε-amino group of N-benzyl-
oxycarbonyllysine methyl ester at the triple bond of
alkynones under basic conditions [12]. Reactions of
propynals with alanine or lysine or their esters were
not reported.
CH=N protons, while the spectra of the products
obtained from benzaldehyde contained one (alanine
derivative) or two signals (lysine derivative). In the IR
spectra of aza enynes Xa and XIa absorption bands at
2170 (C≡C), 1730–1750 (C=O), 1610 (C=N), and
1240–1250, 830– 850 cm–1 (Si–C) were observed.
Silicon-containing acetylenic Schiff bases Xa and
XIa are readily modifiable polyfunctional analogs of
natural compounds having several pharmacophoric
groups. Silicon-containing acetylenic aldehyde imines
were successfully used as key intermediate products in
the synthesis of thienomycins [14]. In recent years,
reversible formation of azomethine bond is widely
utilized in dynamic covalent chemistry [15].
We previously showed that N-silylated amino acid
silyl esters (generated in situ by the action of excess
hexamethyldisilazane on the initial amino acids in the
presence of a catalytic amount of concentrated sulfuric
acid) were very efficient in the synthesis of 3-trimeth-
ylsilylprop-2-ynamides by acylation with trimethyl-
silylpropynoyl chloride [13]. However, our attempt to
obtain Schiff base Me3SiC≡CCH=NCH(Me)COOH
(VIII) by reaction of N,O-bis(trimethylsilyl) derivative
of alanine with an equimolar amount of trimethylsilyl-
propynal in benzene at room temperature resulted in
isolation of an orange–red powder-like oligomer which
was readily soluble in most organic solvents, including
benzene. The IR spectrum of the product contained
broadened absorption bands at 3400 (O–H), 2080
(C≡C), 1730, 1670, 1615 (C=O, CH=N), and 1245,
840 cm–1 (Me3Si). Its molecular weight determined by
cryoscopy in benzene corresponded to four fragments
of the expected Schiff base. The product was para-
magnetic (according to the ESR data), and the spectral
parameters indicated the presence of an extended con-
jugation chain in its molecule. Additional physico-
chemical studies are necessary to determine its
structure.
Thus the nature of primary amine may be a crucial
factor responsible for chemoselectivity of their addi-
tion to substituted propynals and product structure. The
newly synthesized polyfunctional acetylene deriva-
tives, acetylenic aminals and Schiff bases, may be used
as building blocks in fine organic synthesis, biologi-
cally active compounds, and multidentate ligands for
metal complex catalysis. Microwave irradiation en-
sures considerably shortened reaction time, the high
yields and chemoselectivity being conserved.
EXPERIMENTAL
The IR spectra were recorded on a Bruker IFS-25
spectrometer, and the Raman spectra were obtained on
a Bruker Vertex-70 instrument equipped with a Raman
1
13
module. The H and C NMR spectra were measured
on a Bruker DPX-400 spectrometer at 400.13 and
101.62 MHz, respectively, using hexamethyldisiloxane
as internal reference. The ESR spectra were recorded
at room temperature on a Radiopan SE/X-2547 radio-
spectrometer (sensitivity 5×1010 spin/g) equipped with
a magnetometer and a high-frequency meter. The con-
centration of paramagnetic centers was calculated
according to the procedure described in [16] using
diphenylpicrylhydrazyl as calibration standard and
double integration nomogram of the absorption curve
derivative [17]. The progress of reactions was moni-
tored by TLC on Silufol UV-254 plates using chloro-
form–methanol (3:1) as eluent. Microwave-assisted
syntheses were carried out in an unmodified LG MS-
1904H furnace (700 W); the temperature therein was
measured after the end of irradiation using an IR
C-20.1 pyrometer. 3-Trimethylsilylprop-2-ynal was
synthesized according to the procedure reported in
[18], 3-phenylprop-2-ynnal was prepared as described
in [19], and 2-aminopyrimidines were commercially
Trimethylsilylpropynal (Ia) reacted with D,L-α-
amino acid (alanine and lysine) methyl esters IXa and
IXb (generated in situ from the corresponding hydro-
chlorides by the action of triethylamine) at room tem-
perature (4 h) to give previously unknown acetylenic
Schiff bases Xa and XIa in 69–83% yield (Scheme 3).
The reactions were chemoselective, and only the alde-
hyde group in initial acetylenic aldehyde Ia was in-
volved. Unlike trimethylsilylpropynal (Ia), benzalde-
hyde (Ic) reacted with alanine and lysine methyl esters
IXa and IXb in stereoselective fashion, and the result-
ing Schiff bases Xa and XIa were obtained as single,
assumingly E isomers. The Schiff bases obtained from
alanine and lysine methyl esters and trimethylsilyl-
propynal displayed in the 1H NMR spectra two or four
signals, respectively, belonging to the azomethine
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

MAREEV et al.
1548
3
available products. D,L-α-Amino acid methyl esters
were synthesized according to [20]. The solvents were
purified by fractional distillation prior to use.
(6H, CH3), 6.28 d (2H, 5-H, J = 5.0 Hz), 6.45 t (1H,
3
NCHN, J = 8.2 Hz), 6.63 d (2H, NH), 7.99 d (2H,
4-H). 13C NMR spectrum (CDCl3), δC, ppm: –0.49
(Me3Si), 23.63 (CH3), 51.35 (NCHN), 85.27 (SiC≡),
103.43 (≡CCH), 110.77 (C5), 156.89 (C6), 160.21 (C2),
167.12 (C4). Found, %: C 58.52; H 6.50; N 25.90;
Si 8.39. C16H22N6Si. Calculated, %: C 58.86; H 6.79;
N 25.74; Si 8.60.
N,N′-Bis(pyrimidin-2-yl)-3-trimethylsilylprop-2-
yne-1,1-diamine (IVa). An ampule was charged with
a solution of 0.405 g (3.208 mmol) of aldehyde Ia,
0.305 g (3.208 mmol) of 2-aminopyrimidine (IIa),
0.015 g (0.15 mmol, 5 mol %) of hydrochloric acid
(c = 11.7 M), and 0.194 g of water in 1.27 ml of tert-
butyl alcohol. The ampule was sealed and kept for
7 days at 25°C with intermittent shaking (method a),
or subjected to microwave irradiation in 2–4-min
pulses over a period of 18 min (700 W, 70–90°C) with
subsequent cooling to room temperature (method b), or
heated for 2.5 h at 90°C (method c). The ampule was
opened, and the solvent was removed on a rotary
evaporator to obtain a mixture of compound IVa and
unreacted aminopyrimidine IIa.
N,N′-Bis(pyrimidin-2-yl)-3-phenylprop-2-yne-
1,1-diamine (IVc). A mixture of 0.275 g (2.11 mmol)
of phenylpropynal (Ib), 0.2 g (2.11 mmol) of 2-amino-
pyrimidine (IIa), 0.009 g of hydrochloric acid (c =
11.7 M), 0.1 ml of water, and 2.0 ml of tert-butyl
alcohol was stirred for 7 days at room temperature.
Crystals gradually separated from the solution and
were filtered off, washed with cold methylene chloride
(2 ml), and dried under reduced pressure. Yield 0.139 g
(44%), light brown powder. Evaporation of the mother
liquors gave an additional amount of the product,
0.274 g, which was purified as described above to
isolate 0.116 g of aminal IVc. Overall yield 80%,
mp 179–181°C. IR spectrum (KBr), ν, cm–1: 3410
(NH); 1590, 1530, 1500 (C=C, C=N); 1570 (δNH).
Aminal IVa was purified as follows. The product
mixture, 0.323 g, was treated with 10 ml of water and
2 ml of diethyl ether, the mixture was stirred for
30 min at room temperature, and the precipitate was
filtered off, washed with 10 ml of diethyl ether, and
dried under reduced pressure until constant weight.
Yield 85 (a), 83 (b), 60% (c); mp 166–164°C. IR spec-
trum (KBr), ν, cm–1: 3220 (NH); 2165 (C≡C); 1560,
Raman spectrum: ν 2236 cm–1 (C≡C). H NMR spec-
trum (DMSO-d6), δ, ppm: 6.67 t (2H, 5-H), 6.93 t (1H,
NCHN), 7.31–7.37 m (5H, NH, p-H, m-H), 7.58 d
(2H, o-H, J = 7.59 Hz), 8.34 d (4H, 4-H, 6-H, J =
8.35 Hz). 13C NMR spectrum (DMSO-d6), δC, ppm:
51.31 (NCHN), 80.44 and 88.90 (C≡C), 111.66 (C5),
122.46 (Ci), 128.46 (Cp, Cm), 131.56 (Co), 158.01 (C4,
C6), 160.66 (C2). Found, %: C 67.06; H 4.48; N 27.26.
C19H16N4. Calculated, %: C 67.54; H 4.67; N 27.80.
1
3
3
1
1585 (C=N, C=C); 1220, 815 (Si–CH3). H NMR
spectrum, δ, ppm: in CDCl3: 0.08 s (9H, Me3Si), 6.71 t
3
3
(2H, 5-H, J = 4.7 Hz), 6.74 t (1H, NCHN, J =
7.9 Hz), 7.65 d (2H, NH), 8.35 d (4H, 4-H, 6-H); in
3
DMSO-d6: 0.10 s (9H, Me3Si), 6.66 t (2H, 5-H, J =
3
4.8 Hz), 6.69 t (1H, NCHN, J = 9.0 Hz), 7.29 d (2H,
NH), 8.28 d (4H, 4-H, 6-H). 13C NMR spectrum
(DMSO-d6), δC, ppm: –0.27 (Me3Si), 50.65 (NCHN),
84.29 (SiC≡), 104.72 (≡CCH), 111.40 (C5), 157.73
(C4, C6), 160.20 (C2). Found, %: C 56.01; H 6.46;
N 28.07; Si 9.58. C14H18N6Si. Calculated, %: C 56.35;
H 6.08; N 28.16; Si 9.41.
Reaction of D,L-alanine with 3-trimethylsilyl-
prop-2-ynal. A mixture of 0.23 g (2.6 mmol) of
D,L-alanine, 0.82 g (5.2 mmol) of hexamethyldisila-
zane, and a catalytic amount of concentrated sulfuric
acid was heated for 20 min under reflux. Excess hexa-
methyldisilazane was removed under reduced pressure,
8 ml of anhydrous benzene, 0.32 g (2.5 mmol) of tri-
methylsilylpropynal (Ia), and 0.25 g of MgSO4 were
added to the residue, and the resulting suspension was
stirred for 24 h at room temperature; the mixture
turned dark red and homogeneous. The solution was
treated with 3 ml of water and extracted with diethyl
ether (3×5 ml), and the extract was dried over MgSO4
and concentrated under reduced pressure to isolate
0.197 g of a dark red substance with mp 100–103°C,
which was soluble in organic solvents and insoluble in
water. IR spectrum (KBr), ν, cm–1: 3400 br, 2950,
2890, 2080 br, 1730 sh, 1670 sh, 1615 br, 1400 br,
1245 br, 1050 br, 840 sh, 825 v.s, 745, 695, 630 v.s.
N,N′-Bis(4-methylpyrimidin-2-yl)-3-trimethyl-
silylprop-2-yne-1,1-diamine (IVb) was synthesized
according to method a from 0.706 g (5.59 mmol) of
aldehyde Ia and 0.605 g (5.59 mmol) of 4-methyl-
pyrimidin-2-amine (IIb) in a mixture of 0.383 g of
water, 0.028 g (0.28 mmol, 5 mol %) of hydrochloric
acid (c = 11.7 M), and 2.2 ml of tert-butyl alcohol. The
product was purified as described above for IVa. Yield
0.639 g (70%), colorless powder, mp 174–176°C. IR
spectrum (KBr), ν, cm–1: 3260 (NH); 2170 (C≡C);
1500, 1580 (C=C, C=N); 1250, 830 (Si–CH3). Raman
1
spectrum, ν, cm–1: 2167 (C≡C), 1572 (C=N). H NMR
spectrum (CDCl3), δ, ppm: –0.05 s (9H, Me3Si), 2.15 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

CHEMOSELECTIVE REACTIONS OF TRIMETHYLSILYLPROPYNAL
1549
13
ESR spectrum: N = 1.5×1017 spin/g, g = 2.0039, ΔH =
8.4 Oe, A/B = 1.1, singlet. Found, %: C 59.72; H 7.33;
N 7.57; Si 17.45. M 786 (by cryoscopy in benzene).
The elemental composition and molecular weight
corresponded to four molecules of Schiff base
Me3SiC≡CCH=NCH(Me)COOH (VIII), M 197.31.
and 7.52 s (2H, CH=N). C NMR spectrum (CDCl3),
δC, ppm: –0.72, –0.64, –0.60 (Me3Si); 23.24, 23.31,
23.46 29.88, 29.91, 30.72, 32.70, 32.74, 33.10 (CH2);
51.93, 51.95, 52.06, 52.08, 55.58 (OCH3); 61.63, 61.69
(CH2N); 67.48, 67.60, 73.43, 73.52 (CHN); 95.85,
95.88, 96.28, 96.30, 96.97, 97.08, 99.63, 99.72,
100.71, 100.73, 101.31, 101.34, 104.08, 104.21,
105.45, 105.57 (C≡C); 142.69, 142.79, 144.66, 144.67,
144.75, 144.76, 147.13, 147.22 (CH=N); 171.26,
171.31, 171.94, 171.99 (C=O). 29Si NMR spectrum
(CDCl3), δSi, ppm: –16.69, –16.52, –16.34, –16.03.
Found, %: C 60.71; H 8.57; N 7.40; Si 14.23.
C19H32N2O2Si2. Calculated, %: C 60.59; H 8.56;
N 7.44; Si 14.31.
N-(3-Trimethylsilylprop-2-yn-1-ylidene)-
D,L-alanine methyl ester (Xa). A solution of 0.25 g
(2.0 mmol) 3-trimethylsilylprop-2-yn-1-al (Ia) in 1 ml
of anhydrous benzene was added dropwise to a mix-
ture of 0.28 g (2.0 mmol) of D,L-alanine methyl ester
hydrochloride (IXa), 0.2 g (2.0 mmol) of triethyl-
amine, and 0.2 g of calcined MgSO4 in 6 ml of
anhydrous benzene. The mixture was stirred for 4 h at
room temperature and filtered, and the filtrate was
evaporated under reduced pressure. Yield 0.29 g
(69%), red viscous liquid. IR spectrum (film), ν, cm–1:
2170 (C≡C); 1730 (C=O); 1610 (C=N); 1240, 830
(Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.16 s and
0.17 s (9H, Me3Si), 1.39 d and 1.41 d (3H, CH3CH,
3J = 6.91 Hz), 3.67 s and 3.69 s (3H, CH3O), 3.96 q
and 4.59 q (1H, CHN), 7.47 s and 7.48 s (1H, CH=N).
13C NMR spectrum (CDCl3), δC, ppm: –0.58 (CH3Si),
18.54 and 19.14 (CHCH3), 52.20 and 52.31 (OCH3),
62.80 and 68.24 (CHN); 95.62, 99.91, 100.94, 105.93
(C≡C); 144.46 and 147.05 (CH=N), 171.90 and 172.82
(C=O). 29Si NMR spectrum (CDCl3), δSi, ppm: –15.94,
–15.59. Found, %: C 56.67; H 7.85; N 6.63; Si 12.99.
C10H17NO2Si. Calculated, %: C 56.83; H 8.11; N 6.63;
Si 13.29.
N-Benzylidene-D,L-alanine methyl ester (Xb).
A suspension of 0.209 g (1.50 mmol) of D,L-alanine
methyl ester hydrochloride (IXa), 0.152 g (1.50 mmol)
of triethylamine, and 2.0 g of MgSO4 in 5 ml of ben-
zene was stirred for 1 h at 25°C, 0.159 g (1.5 mmol) of
benzaldehyde (Ic) was added, and the mixture was
stirred for 24 h. The mixture was filtered, the precip-
itate was washed with benzene (5×15 ml), the filtrate
was combined with the washings, and the solvent was
removed under reduced pressure. Yield 0.178 g (62%),
yellow oily substance. IR spectrum (film), ν, cm–1:
1736 (C=O); 1643 (C=N); 1580, 1600 (C=Carom).
1H NMR spectrum (CDCl3), δ, ppm: 1.51 d (3H,
CH3CH, 3J = 6.72 Hz), 3.73 s (3H, CH3O), 4.15 q (1H,
CH3CH), 7.41 m (3H, p-H, m-H), 7.76 d (2H, o-H,
3J = 7.80 Hz), 8.31 s (1H, CH=N). 13C NMR spectrum
(CDCl3), δC, ppm: 19.62 (CH3CH), 52.34 (CH3O),
68.08 (CH3CH), 128.62 (Cm), 128.75 (Co), 131.28
(Cp), 135.82 (Ci), 163.20 (CH=N), 173.14 (C=O).
N2,N6-Dibenzylidene-D,L-lysine methyl ester
(XIb) was synthesized in a similar way from 0.289 g
(1.24 mmol) of D,L-lysine methyl ester dihydrochlo-
ride (IXb) and 0.237 g (2.48 mmol) of benzaldehyde
(Ic) in the presence of 0.251 g (2.48 mmol) of triethyl-
amine and 2.480 g (2.48 mmol) of MgSO4 in 8 ml of
benzene. Yield 0.237 g (57%), yellow oily substance.
IR spectrum (film), ν, cm–1: 1739, 1704 (C=O); 1645,
1621 (C=Carom); 1601, 1580 (C=N). 1H NMR spectrum
(CDCl3), δ, ppm: 1.40 m (2H, CH2), 1.74 m (2H, CH2),
1.92 m (1H, CH2), 2.03 m (1H, CH2), 3.63 m (2H,
CH2N), 3.74 s (3H, CH3O), 4.17 m (1H, CHN), 7.53 m
(6H, p-H, m-H), 7.78 d and 7.84 d (2H each, o-H),
N2,N6-Bis(3-trimethylsilylprop-2-yn-1-ylidene)-
D,L-lysine methyl ester (XIa) was synthesized in
a similar way from 0. 29 g (1.24 mmol) of D,L-lysine
methyl ester dihydrochloride (IXb) and 0.32 g
(2.48 mmol) of 3-trimethylsilylprop-2-yn-1-al (Ia) in
the presence of 0.26 g (2.5 mmol) of triethylamine and
0.2 g of calcined MgSO4 in 6 ml of anhydrous benzene.
Yield 0.34 g (72%), reddish viscous liquid. Analogous
reaction with equimolar amounts of the reactants,
0.41 g (1.76 mmol) of D,L-lysine methyl ester dihydro-
chloride (IXb) and 0.22 g (1.76 mmol) of 3-trimethyl-
silylprop-2-yn-1-al (Ia) in the presence of 0.18 g
(1.76 mmol) of triethylamine and 0.17 g of calcined
MgSO4 in 8 ml of anhydrous benzene, gave 0.27 g
(83%) of Schiff base XIa. IR spectrum (film), ν, cm–1:
2170 (C≡C); 1750 (C=O); 1610 (C=N); 1250, 850
1
13
(Si–C). H NMR spectrum (CDCl3), δ, ppm: 0.143 s,
8.39 s and 8.48 s (1H each, CH=N). C NMR spec-
0.150 s, 0.156 s, and 0.159 s (18H, Me3Si); 1.26 m,
1.58 m, 1.76 m, and 1.87 m (6H, CH2); 3.41 m and
3.56 m (4H, CH2N); 3.66 s and 3.67 s (3H, CH3O);
3.78 m and 4.54 m (1H, CHN); 7.41 s, 7.42 s, 7.51 s,
trum (CDCl3), δC, ppm: 23.58 (CH2), 30.63 (CH2),
33.13 (CH2), 52.36 (CH3O), 60.79 (CH2N), 72.41
(CHN); 128.36, 128.77, 129.17, 129.28 (Co, Cm);
131.03 and 131.70 (Cp), 136.23 and 136.78 (Ci),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

MAREEV et al.
1550
9. Baikalova, L.V., Zyryanov, I.A., Afonin, A.V., and
Trofimov, B.A., Russ. J. Org. Chem., 2002, vol. 38,
p. 1674.
161.14 and 164.09 (CH=N), 172.61 (C=O). Found, %:
C 75.22; H 7.30; N 8.09. Calculated, %: C 74.97;
H 7.19; N 8.33. C21H24N2O2.
10. Koroleva, E.V., Gusak, K.N., and Ignatovich, Zh.V.,
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-01024-a).
Usp. Khim., 2010, vol. 79, p. 720.
11. Loh, T.P., Ho, D.S.C., Xu, K.C., and Sim, K.Y., Tetra-
hedron Lett., 1997, vol. 38, p. 865.
12. Crisp, G.T. and Millan, M.J., Tetrahedron, 1998, vol. 54,
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