Synthesis and some chemical properties of 2,2-dimethyl-4-R-1-oxa-4-aza-2-sila-5-benzocycloheptanones

Article abstract of DOI:10.1023/A:1014871813405

One-pot synthesis of 2,2-dimethyl-4-R-1-oxa-4-aza-2-sila-5- benzocycloheptanones (R = Me, CH₂SiMe₂Cl) from the N-methylamide of salicylic acid and salicylamide, respectively, by treatment of these amides with a mixture of hexamethyld

Full text of DOI:10.1023/A:1014871813405

Chemistry of Heterocyclic Compounds, Vol. 38, No. 1, 2002
SYNTHESIS AND SOME CHEMICAL
PROPERTIES OF 2,2-DIMETHYL-
4-R-1-OXA-4-AZA-2-SILA-
5-BENZOCYCLOHEPTANONES*
O. A. Zamyshlyaeva1, A. G. Shipov1, E. P. Kramarova1, Vad. V. Negrebetsky1, A. N. Shumskii2,
S. N. Tandura2, S. Yu. Bylikin1, Yu. E. Ovchinnikov3, S. A. Pogozhikh3, and Yu. I. Baukov1
One-pot synthesis of 2,2-dimethyl-4-R-1-oxa-4-aza-2-sila-5-benzocycloheptanones (R
=
Me,
CH2SiMe2Cl) from the N-methylamide of salicylic acid and salicylamide, respectively, by treatment of
these amides with a mixture of hexamethyldisilazane and dimethylchloromethylchlorosilane was
developed. The hydrolysis and other nucleophilic substitution reactions of the resultant seven-
membered silacyclanes were studied. In the case of the silacyclane with R = Me, hydrolysis leads to the
corresponding disiloxane, while the silacyclane with R = CH2SiMe2Cl gives either 2,2,6,6-tetramethyl-
4-(2-hydroxybenzoyl)-2,6-disilamorpholine or its hydrochloride, depending on the reaction conditions.
The chlorine atom was replaced by fluorine in the silacyclane with R = CH2SiMe2Cl. The structures of
2,2,6,6-tetramethyl-4-(2-hydroxybenzoyl)-2,6-disilamorpholine and its hydrochloride as well as
2,2-dimethyl-4-R-1-oxa-4-aza-2-sila-5-benzocycloheptanones (R = CH2SiMe2Cl, CH2SiMe2F) were
confirmed by X-ray diffraction.
Keywords:
1-oxa-4-aza-2-silacyclanes,
hexamethyldisilazane–dimethylchloromethylchlorosilane
system, pentacoordinated silicon compounds, intramolecular coordination.
We have already described the general strategy for the synthesis of 1-oxa-4-aza-2-silacyclanes including
2-sila-5-morpholinones and 4-acyl-2-silamorpholines [1-3], 4-acyl-2,6-disilamorpholines [1, 4], and 4-acyl-2,6-
disilapiperazines [5] using unsaturated and functionally-substituted amides of carboxylic acids and
dimethylchloromethylchlorosilane as the cyclosilylmethylating agent. The formation of the silacyclanes
proceeds through pentacoordination silicon intermediates [1-5], which are highly reactive in nucleophilic
substitution reactions relative to model compounds with tetrahedral silicon [6]. The scope of this reaction is not
exhausted by the synthesis of six-membered silacyclanes and it may be employed to obtain seven-membered
ring analogs, which hold interest in their conformational structure, chemical behavior, and biological activity.
Thus, the cyclosilylmethylation of salicylamide derivatives gave 2,2-dimethyl-4-(2-trimethylsiloxyethyl)-1-oxa-
4-aza-2-sila-5-benzocycloheptanone, which is a potential corrector of adaptational mechanisms [3], and
_______
* Dedicated to Academician M. G. Voronkov on the occasion of his eightieth birthday.
__________________________________________________________________________________________
1
Russian State Medical University, 117869 Moscow; e-mail: baukov.rgmu@mtu-net.ru. 2 N. D. Zelinsky
3
Institute of Organic Chemistry, 117913 Moscow; e-mail: stas@oic.ac.ru. A. N. Nesmeyanov Institute of
Organoelement Compounds, Russian Academy of Sciences; e-mail: ovchinn@mailru.com. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 1, pp. 127-139, January, 2002. Original article submitted November 4, 2000.
116
0009-3122/02/3801-0116$27.00©2002 Plenum Publishing Corporation

2,2,4-trimethyl-1-oxa-4-aza-2-sila-5-benzocycloheptanone [7]. We should note the recently reported synthesis of
seven-membered silaheterocycles, namely, benzosilaoxaazaheptane and silaspirane, upon the action of Me2SiCl2
or SiCl4 on the C,O-lithium derivative of N-methyl-N-phenylcolamine [8].
In a continuation of studies on silicon derivatives of salicylamide, we describe a one-step method for the
N-chlorosilylmethylation and cyclization of the amide or N-methylamide of salicylic acid by the
hexamethyldisilazane–dimethylchloromethylchlorosilane system.
Use of the hexamethyldisilazane–dimethylchloromethylchlorosilane system, which we have already
proposed for the N-chlorosilylmethylation of amides and lactams [9], in cyclosilylmethylation reactions
simplifies the synthesis of 2-sila-5-morpholinones and 2-sila-4-acylmorpholines by the direct introduction of
amides of α-hydroxycarboxylic acids and N-acylcolamides [1]. Analogously, heating N-methylsalicylamide
with a mixture of hexamethyldisilazane and dimethylchloromethylchlorosilane gave 2,2,4-trimethyl-1-oxa-4-
aza-2-sila-5-benzocycloheptanone (1) in a single step and high yield. This compound was obtained in our
previous
work
in
the
reaction
of
N,O-bis(trimethylsilyl)-N-methylsalicylamide
with
dimethylchloromethylchlorosilane [7].
O
Me
CONHMe
OH
N
(Me3Si)2NH, ClCH2SiMe2Cl
–Me3SiCl, NH4Cl
Me
Me
Si
O
1
In contrast to other silacyclanes containing an O–Si bond [10], silacyclane 1 does not undergo
oligomerization upon storage. Thus, samples of this compound stored for more than a year at room temperature
do not show spectral evidence of oligomerization and the molecular mass determined cryoscopically is virtually
identical to the calculated value (Mexp = 222.2, Mcalc = 221.33). This compound proved unreactive relative to
electrophilic reagents such as Me3SiCl, acetyl chloride, benzoyl chloride, and acetic anhydride upon heating up
to 120°C. However, silacyclane 1 readily reacts with methylmagnesium iodide to give N-trimethylsilylmethyl-
N-salicylamide (2).
Me
CONCH2SiMe3
+
MeMgI; H2O, H
1
OH
2
Hydrolysis of silacyclane 1 upon heating it in chloroform at reflux with excess of 10% aqueous sodium
carbonate for 5 h is not observed. However, 1 readily dissolved in 10% aqueous KOH upon heating.
Acidification of the resultant solution leads to the isolation of the corresponding disiloxane 3 as white crystals.
Disiloxane 3 was also obtained upon heating a solution of silacyclane 1 in 1:1 acetonitrile–water at reflux.
Me
O
Me
O
2
N
CONCH2SiMe2
MeCN, H2O
–H2O
2
Me
Me
OH
Si
O
1
3
117

A special feature of disiloxane 3 is its tendency to undergo dehydration upon heating to give starting
silacyclane 1. In particular, this transformation occurred in an attempt to fractionate disiloxane 3 in vacuum.
Treatment
of
salicylamide
with
an
excess
of
the
hexamethyldisilazane–
dimethylchloromethylchlorosilane system gave 2,2-dimethyl-4-(dimethylchlorosilylmethyl)-1-oxa-4-aza-2-sila-
5-benzocycloheptanone (4), which contains one tetracoordinated silicon atom and one pentacoordinated silicon
atom (Scheme 1).
Scheme 1
Cl
H
Me
Si
(Me3Si)2NH /
ClCH2SiMe2Cl
CONH2
OH
O
C
Me
H2O
O
N
Si
Me
OH
Me
.
HCl
5
Me
Si
Me
O
Cl
H2O, NaHCO3
SOCl2
N
1. MeOH, (Me3Si)2NH
Me
Me
.
2. BF3 Et2O
Si
O
Me
Me
Si
Me
F
4
Me
Me
Si
O
O
O
N
C
N
Si
Me
OH
Me
Si
O
5
6
Me
Evidence for the existence of an intramolecular O→Si coordination bond in 4 was found in the IR bands
at 1600 and 1523 cm-1 and the corresponding signals in the 1H, 13C, and 29Si NMR spectra (Table 1, see the data
of our previous work [11]) as well as in X-ray diffraction analysis.
In contrast to silacyclane 1, the hydrolysis of chloride 4 readily proceeds upon its treatment in
chloroform solution with aqueous sodium bicarbonate and leads to 2,2,6,6-tetramethyl-4-(2-hydroxybenzoyl)-
2,6-disilamorpholine (5) by analogy to the hydrolysis or aminolysis of N,N-bis(dimethylchlorosilyl-
methyl)amides [2, 5].
Disilamorpholine 5 may also be obtained by a one-pot method from salicylamide upon heating it at
reflux with an excess of the hexamethyldisilazane–dimethylchloromethylchlorosilane system and subsequent
hydrolysis of resultant chloride 4 without its isolation. However, disilamorpholine 5 readily reconverts to
chloride 4 upon treatment with thionyl chloride.
The signals of the SiMe2 and NCH2 groups in the 1H NMR spectra of compound 5 in deuterochloroform
at -60°C appear as two pairs of singlets with equal intensity (Table 1). Warming to room temperature leads to
the consecutive broadening of these signals and coalescence into two singlets with averaged chemical shift.
Lowering the temperature restores the original spectrum. The observed dynamic process is characteristic for
hindered rotation about the amide bond. The barrier for this process established by a dynamic NMR method was
11.3 kcal/mole relative to NCH2 and 11.6 kcal/mole relative to SiMe2. In the case of PhC(O)NMe2, this barrier
118

TABLE 1. 1H, 13C and 29Si NMR Spectra of 4-6
29Si,
Com-
pound
δ 1H, ppm.
CH3 CH2
δ
13C, ppm
C(O)
δ
ppm
CH3
-2.46
CH2
Ar
0.39 3.10
39.74
170.58
152.62 C(O);
121.29 C(CO)
30.4
4
0.68*
0.22
3.00*
3.20
7.24*
0.06
47.70*
41.05
121.78; 122.96;
-36.3*
9.7
130.72; 134.12
169.97
169.48
158.15 C(O);
117.98; 118.32;
118.40; 127.95;
131.83
5
6
0.39*
2.95
-2.58
39.97
152.01 C(O);
28.6
124.11 C(CO)
0.38*
2.73*
1.63*
43.09*
121.38; 122.84;
130.57; 132.88
-17.0*
(7.8)*2
(22.9)*2
(40.0)*2
(237.8)*2
_______
* Group or atom attached to the pentacoordinated silicon atom or signal of
the pentacoordinated silicon atom.
*2 Coupling constant with the fluorine atom.
is 15.3 kcal/mole [12]. The difference in the hindered rotation barrier by almost 4 kcal/mole is apparently
related to several factors, one of which may be the difference in the acidity of the medium in solutions of 5,
which contains a phenolic hydroxyl group.
The hydrolysis of chloride 4 by atmospheric moisture upon its prolonged storage under conditions
excluding an external acceptor of hydrogen chloride led to the formation of the 2,2,6,6-tetramethyl-4-(2-
hydroxybenzoyl)-2,6-disilamorpholine hydrochloride (5·HCl). An X-ray diffraction of this hydrochloride
indicated that the oxygen atom of the amide group undergoes protonation rather than the oxygen atom of
disiloxane fragment. This behavior is analogous to that observed for adducts of 4-acyl-2,6-disilamorpholines
with strong acids [13].
Replacement of the chlorine atom in 4 by a fluorine atom with retention of the silacyclane fragment was
carried out by its consecutive treatment with a mixture of methanol and hexamethyldisilazane and then with
BF3·Et2O (see scheme 1). This reaction probably proceeds through the intermediate formation of the
corresponding silylmethoxide, which, upon treatment with BF3·Et2O, is converted into the final product,
2,2-dimethyl-4-(dimethylfluorosilylmethyl)-1-oxa-4-aza-2-sila-5-benzocycloheptanone (6).
The existence of a pentacoordinated silicon atom in fluoride 6 was established using its spectral data
(see Table 1) and an X-ray diffraction investigation.
Bicyclic derivatives 4 and 6 contain a pentacoordinated silicon atom in five-membered chelate ring
C(O)CH SiMe X
. The hypervalent X–Si(C3)–O (X = Cl, F) in these compounds was studied in detail for
2
2
lactams and amides of carboxylic acids [11]. A feature of compounds 4 and 6 is a seven-membered ring
condensed at the N–C bond, which is considered a medium-sized ring with increased internal energy (strain).
However, this addition does not introduce any significant changes in the nature of hypervalent bonding in this
fragment. The NMR spectral parameters for 4 and 6 in low-polarity solvents at low concentration and room
temperature indicate intramolecular C=O→Si coordination. Thus, two signals are seen in the 29Si NMR
spectrum of each compound. The downfield chemical shifts (30.4 ppm for 4 and 28.6 ppm for 6) are
characteristic for XCH2SiMe2OAr derivatives and correspond to a tetracoordinated silicon atom. The two other
signals (-36.3 for 4 and -17.0 for 6) are considerably shifted upfield relative to model tetracoordinated
XCH2SiMe2Y compounds, for which shielding of the silicon atom is in the range 25±5 ppm, i.e., the second
silicon atom in these compounds is pentacoordinated. Similar values for the pentacoordinated silicon atom
119

δSi = -39.0 ppm were observed in bis(N-dimethylchlorosilylmethyl)acetamide CH3C(O)N(CH2SiMe2Cl)2, while
δSi = 26.8 ppm in CDCl3 at 20°C for the second tetracoordinated silicon atom in an analogous environment [14].
The pentacoordinated silicon atom in compound 6 has δSi = -17.0 ppm, which is similar to the chemical
shifts of the hypervalent silicon atom in bis(N-dimethylfluorosilylmethyl)acetamide CH3C(O)N(CH2SiMe2F)2,
δSi = -23.5 ppm, while δSi = 29.0 ppm for the tetrahedral silicon in the same molecule [14]. The decrease in
shielding of the 29Si nucleus by 19.2 ppm in going from chloro derivative 4 (δSi = 36.3 ppm) to fluoro derivative
6 (δSi = -17.0 ppm) is analogous to that observed for N-(dimethylhalosilylmethyl)-N-(1-phenylethyl)acetamide
in CDCl3 at 20°C (δSi = 18.8 ppm) [15, 16]. Furthermore, the lower direct coupling constant 1JSiF = 237.8 Hz for
6 relative to values 270-290 Hz characteristic for tetracoordinated organosilicon compounds also suggests
pentacoordination of the silicon atom.
13
Comparison of the C NMR spectra for compounds 4 and 6 (see Table 1) shows that replacement of a
chlorine atom by a fluorine atom leads to increased shielding of the carbon atoms in the SiMe2, SiCH2, and C=O
groups by ∆δ13C = -5.61 (1.63 - 7.24), -4.61 (43.09 - 47.70), and -1.10 (169.48 - 170.58) ppm, respectively.
Analogous behavior is found for O–Si-chelated N-(dimethylhalosilylmethyl)-N-(1-phenylethyl)acetamides:
∆δ13C = -5.44, -4.53, -1.58 ppm, respectively, in CDCl3 at 20°C [16].
The 1H NMR spectra correspond to the proposed structures 4-6 (see Table 1 and Experimental).
An X-ray diffraction of halides 4 and 6 showed that one of the two silicon atoms in these compounds is
pentacoordinated (Si(1)) while the other is tetracoordinated (Si(2)). The analogs differ only in the halo substituent
at the pentacoordinated silicon atom (Cl in 4 and F in 6). Nevertheless, these molecules display somewhat
different conformations in the crystal although the space groups are the same and the unit cell parameters are
quite similar (Table 2).
TABLE 2. Major X-ray Diffraction Parameters for 4, 5, 5·HCl, and 6
Parameters
5·HCl
4
5
6
Empirical formula C13H20ClNO2Si2
C13H21NO3Si2
290
C13H22ClNO3Si2
100
8.036(4)
9.674(4)
22.00(1)
90
99.16(1)
90
1689(1)
1.306
C13H20FNO2Si2
130
10.592(5)
14.075(5)
11.524(5)
90
114.50(3)
90
1563(1)
1.264
T, K
210
a, Å
12.390(4)
10.386(3)
12.524(4)
90
95.48(2)
90
9.394(6)
12.843(7)
15.142(9)
109.37(4)
98.89(5)
105.28(5)
1603(2)
b, Å
c, Å
α, deg.
β, deg.
γ, deg.
V, Å3
1604.2(8)
1.300
d
calc, g·cm-3
1.225
Space group, Z
2θmax(°)
P21/c, (4)
52
P
, (4)
P21/n, (4)
58
P21/c, (4)
52
1
48
Scanning
ω/2θ
θ/2θ
ω/2θ
θ/2θ
Number of
measured
reflections
3247
5081
10338
3051
Number of
3101
252
4671
351
3941
269
2883
252
reflections in least
squares calculation
Number of
parameters in least
squares calculation
Absorption
3.85
2.25
3.74
2.35
coefficient, cm-1
R1(I >2σ(I))
0.036
0.096
0.080
0.258
0.078
0.121
0.040
0.106
wR2 (all
reflections)
120

Some difference in the conformations is attributed to the shape of the central seven-membered
heterocycle. The torsion angles of the C(10)–O(2)–Si(2)–C(13) differ by 16-26° in these analogs. However, the twist
form of this heterocycle with an approximate two-fold axis traversing through Si(2) and the midpoint of the
C(4)–C(5) bond is the same in these molecules. These conformational differences presumably arise due to the
high flexibility of the heterocycle fragment containing the oxygen atom.
On the other hand, the major differences in molecular packing in the crystals of 4 and 6 should be
ascribed to the large difference in the Si–Cl and Si–F bond lengths (0.65 Å) and the difference in the van der
Waals radii of the chlorine and fluorine atoms (0.4 Å), which leads to a considerable difference in the shape of
these molecular analogs in the vicinity of the hypervalent fragment. Despite the difference in packing, a
characteristic approximation of the halogen atoms and Si(2) of the adjacent molecule is observed. Specifically,
the chlorine and fluorine atoms are found opposite to the Si(2)–O(2) bond at distances of 3.86 and 3.31 Å from the
silicon atom, which are similar to the corresponding sums of the van der Waals radii (3.8 Å for Cl and Si and
3.4 Å for F and Si) [17]. The crystal of chloride 4 consists of centrosymmetric "dimers" (see Fig. 1), while the
analogously contacting molecules in the crystal of fluoride 6 form infinite chains (see Fig. 2). The electrostatic
Si···halogen interaction is rather clearly evident here. The slight positive charge on Si(2) is due to the polarity of
the Si–O bond. However, the slight lengthening of the Si(2)–O(2) bond by 1.67 Å in the structures of 4 and 6
relative to the usual values 1.63-1.64 Å (for example, in the structures of 5 and 5·HCl, see Tables 3 and 5) is
evidently due to very weak intermolecular Hal→Si coordination interactions. The larger expansion of the
coordination tetrahedron of Si(2) in 4 and 6 toward O(2)–Si(2) ···Hal than in 5 and 5·HCl also indicates such an
interaction (the Si(2)–C(11)–C(12)–C(13) torsion angle in 4 and 6 is 10-17° greater than in 5 and 5·HCl).
Fig. 1. Molecular structure of 4 in the crystal. Hydrogen atoms are not shown.
The short Si···Cl contacts of adjacent molecules are shown by dashed lines.
TABLE 3. Main Bond Lengths (l) in 4 and 6
l, Å
l, Å
Bond
Bond
4
6
4
6
Cl(1)–Si(1)
F(1)–Si(1)
Si(1)–O(1)
2.308(1)
Si(2)–O(2)
O(1)–C(4)
N(1)–C(4)
1.671(2)
1.278(2)
1.316(2)
1.673(2)
1.259(2)
1.332(3)
1.672(2)
2.158(2)
1.961(1)
121

TABLE 4. Main Bond Angles (ω) in 4 and 6
ω, deg.
ω, deg.
Angle
Angle
4
6
4
6
Cl(F)(1)–Si(1)–C(1)
Cl(F)(1)–Si(1)–C(2)
C(1)–Si(1)–C(2)
Cl(F)(1)–Si(1)–C(3)
C(1)–Si(1)–C(3)
C(2)–Si(1)–C(3)
Cl(F)(1)–Si(1)–O(1)
C(1)–Si(1)–O(1)
94.2(1)
93.7(1)
118.5(1)
88.0(1)
119.6(1)
121.6(1)
170.81(5)
91.1(1)
98.5(1)
96.9(1)
117.9(1)
92.0(1)
120.6(1)
118.5(1)
171.2(1)
86.0(1)
C(2)–Si(1)–O(1)
C(3)–Si(1)–O(1)
O(2)–Si(2)–C(12)
O(2)–Si(2)–C(11)
C(12)–Si(2)–C(11)
O(2)–Si(2)–C(13)
C(12)–Si(2)–C(13)
C(11)–Si(2)–C(13)
90.3(1)
82.9(1)
87.6(1)
79.2(1)
106.6(1)
110.8(1)
114.6(1)
102.1(1)
113.4(1)
108.6(1)
105.0(1)
110.2(1)
113.9(1)
102.0(1)
113.4(1)
111.4(1)
TABLE 5. Main Bond Lengths in 5 and 5·HCl
l, Å
l, Å
Bond
Bond
5
5
·HCl
5
5·HCl
Si(1)–O(1)
Si(2)–O(1)
O(2)–C(7)
O(3)–C(9)
N(1)–C(7)
1.630(4)
1.640(4)
1.216(7)
1.345(7)
1.340(7)
1.636(3)
1.637(3)
1.292(5)
1.362(5)
1.297(5)
Si(21)–O(21)
O(22)–C(27)
O(23)–C(29)
N(21)–C(27)
1.639(4)
1.240(7)
1.356(7)
1.355(7)
The hypervalent fragments in 4 and 6 have the ordinary distorted trigonal bipyramidal configuration.
The deviations of the silicon atoms from the plane of the equatorial substituents toward the halogen atom (∆Si)
are 0.06 and 0.19 Å, respectively. Thus, the hypervalent O–Si–Hal bond in fluoride 6 is more asymmetric,
which indicates a greater O→Si bond length. The ratios between the lengths of the components of the
hypervalent bonds and parameters ∆Si in these structures are in good accord with the relationships found in our
previous work [18] for pentacoordinated silicon compounds.
Fig. 2. Molecular structure of 6 in the crystal. Hydrogen atoms are not shown.
The short Si···F contact with an adjacent molecule is shown by a dashed line.
122

TABLE 6. Main Bond Angles in 5 and 5·HCl
ω, deg.
ω, deg.
5
Angle
Angle
5
5
·HCl
O(1)–Si(1)–C(1)
O(1)–Si(1)–C(2)
C(1)–Si(1)–C(2)
O(1)–Si(1)–C(5)
C(1)–Si(1)–C(5)
C(2)–Si(1)–C(5)
O(1)–Si(2)–C(3)
O(1)–Si(2)–C(4)
O(1)–Si(2)–C(6)
C(3)–Si(2)–C(6)
C(4)–Si(2)–C(6)
Si(1)–O(1)–Si(2)
110.1(3)
108.8(3)
110.7(4)
105.0(3)
109.9(4)
112.3(3)
108.5(2)
112.2(2)
111.6(3)
105.7(2)
108.0(3)
110.6(2)
112.6(2)
108.1(2)
104.7(2)
107.7(2)
111.9(2)
130.3(2)
O(21)–Si(21)–C(22)
O(21)–Si(21)–C(21)
C(22)–Si(21)–C(21)
O(21)–Si(21)–C(25)
C(22)–Si(21)–C(25)
C(21)–Si(21)–C(25)
O(21)–Si(22)–C(23)
O(21)–Si(22)–C(24)
C(23)–Si(22)–C(24)
O(21)–Si(22)–C(26)
C(23)–Si(22)–C(26)
C(24)–Si(22)–C(26)
Si(21)–O(21)–Si(22)
107.9(3)
111.0(3)
112.3(4)
105.6(3)
112.5(3)
107.4(3)
108.2(3)
109.6(3)
114.0(3)
104.0(3)
110.8(3)
109.8(3)
128.8(3)
105.4(3)
110.4(4)
110.0(3)
129.3(3)
Disilamorpholine 5 and its hydrochloride 5·HCl (Figs. 3 and 4) contain six-membered disiloxane
heterocycles featuring virtually the same chair conformation with a plane of symmetry traversing the oxygen
and nitrogen atoms. The distortion of this symmetry may be evaluated by the difference in absolute values of the
corresponding torsion angles over both sides of this plane and was found to be only 2° and 7° for two
crystallographically independent molecules of 5 and 6° in hydrochloride 5·HCl. The corresponding bond lengths
and angles in the heterocycles of these compounds are very similar (see Tables 5 and 6).
The crystallographically independent molecules in the structure of 5 differ from each other in the
orientation of the plane of the hydroxyphenyl group. Molecule A transforms into B upon rotation of this plane
relative to the C(7)–C(8) bond by 46°. This conformational difference probably provides for denser packing of the
molecules in the crystals by permitting all the OH and C=O groups to participate in hydrogen bonding. The
pairs of molecules A and B form centrosymmetric tetrameric hydrogen-bonded aggregates (Fig. 3). The
hydrogen bond parameters are as follows: O(3)···O(22), 2.77 Å; H(3)···O(22), 1.93 Å; O(3)–H(3)···O(22), 154° and O(23)···O(2a)
,
2.62 Å; H(23)···O(2a), 1.76 Å; O(23)–H(23)···O(2a), 170°. These results indicate medium-strength hydrogen bonds.
Fig. 3. Crystallographically independent part of the centrosymmetric tetrameric hydrogen-bonded aggregate in
the structure of 5. The hydrogen atoms of the OH groups and hydrogen bonds are shown. The atoms with
subscript a belong to the molecules of the second half of the tetramer.
123

Fig. 4. Structure of hydrochloride 5·HCl in the crystal.
The hydrogen atoms in the OH and HCl groups are shown. Cl···HO hydrogen bonds connect
molecules related by a 0.5 – x, 0.5 + y, 0.5 – z screw axis into chains extending along the b-axis.
Only partial, protonation of the C(7)=O(2) group is found in the structure 5·HCl but it leads to lengthening
of this bond by 0.05-0.07 Å relative to the corresponding bond in the structure 5 (see Tables 4 and 5). The
lengths of bonds Cl(1)–H(2) (1.49(3) Å) and O(2)–H(2) (1.39(3) Å) are greater than the usual value in the HCl
molecule and OH group by 0.2 and 0.4 Å, respectively, i.e., this compound should indeed be considered as an
adduct 5·HCl. In addition to this strong bond with a molecule 5, the HCl group forms a hydrogen bond
Cl(1)···H(3a)–O(3a) with an adjacent molecule (see Fig. 3): Cl(1)···O(3a), 3.048(3) Å; Cl(1)···H(3a), 2.22(4) Å;
Cl(1)···H(3a)–O(3a), 170(4)°. These values indicate a medium-strength hydrogen bond. The hydrogen bonds unite
the molecules in the crystal 5·HCl into chains extending along the b-axis. The nature of the intermolecular
contacts in hydrochloride 5·HCl will be discussed in a separate communication.
EXPERIMENTAL
The IR spectra were taken neat or in solution in KBr cells on a two-beam Specord IR-75 spectrometer.
1
The H, 13C, and 29Si NMR spectra were taken for solutions of the sample compounds in CDCl3 on a
Varian XL-400 spectrometer at 400.0, 100.6, and 79.5 MHz, respectively, in a pulse mode with subsequent
Fourier transformation and 2H-stabilization of the resonance conditions using TMS as the internal standard.
2,2,4-Trimethyl-1-oxa-4-aza-2-sila-5-benzocycloheptanone (1). A.
A
sample of dimethyl-
chloromethylchlorosilane (10.2 g, 0.072 mol) was added with stirring to a mixture of N-methylsalicylamide
(10.9 g, 0.072 mol) and hexamethyldisilazane (11.6 g, 0.072 mol) in o-xylene (30 ml). After 5 h heating the
reaction mixture was filtered and the filtrate was evaporated. Fractionation of the residue gave 13.1 g (82%) of
compound 1; bp 180-182°C (8 mm Hg). IR spectrum (CHCl3), ν, cm-1: 1624 (NCO). (Bp 178-180°C (7 mm Hg),
IR spectrum (CHCl3), ν, cm-1: 1624 (NCO) [7]).
B. A sample of 1,1,2,2-tetramethyl-1,2-bis(N-methyl-2-hydroxybenzoylamino)methyl]-1,2-disiloxane
(3) (2.4 g) was added to a distillation flask. Fractionation of this compound in vacuum gave 2.14 g (92%) of
compound 1; bp 179-183°C (8 mm Hg). IR spectrum (CHCl3), ν, cm-1: 1624 (NCO).
N-Methyl-N-trimethylsilylmethylsalicylamide (2). A sample of compound 1 (4.9 g, 0.022 mol) in
ether (30 ml) was added with stirring to a solution of methylmagnesium iodide (3.6 g, 0.022 mol) in ether
(50 ml). After decomposition of the reaction mixture by adding NH4Cl/H2O and distilling off the solvent,
124

recrystallization of the crystalline precipitate from ether gave 4.01 g (77%) of compound 2; mp 142-143°C
1
(ether). H NMR spectrum (CDCl3), δ, ppm: 0.05 (9H, s, SiMe3); 2.99 (2H, s, NCH2Si); 3.35 (3H, s, NMe);
6.40-7.33 (4H, m, C6H4); 9.28 (1H, s, OH). Found, %: C 60.65; H 7.90; N 5.97; Si 11.79. C12H19NO2Si.
Calculated, %: C 60.72; H 8.07; N 5.90; Si 11.83.
2,2-Dimethyl-4-(dimethylchlorosilylmethyl)-1-oxa-4-aza-2-sila-5-benzocycloheptanone (4). A. A
mixture of salicylamide (6.8 g, 0.05 mol), hexamethyldisilazane (19.3 g, 0.12 mol), and
dimethylchloromethylchlorosilane (35.5 g, 0.25 mol) in absolute o-xylene (50 ml) was heated at reflux with
stirring for 10 h. The hot reaction mixture was filtered and the volatile compounds were distilled off. The
residue was recrystallized by adding 20 ml o-xylene to give 17.7 g (76%) of chloride 4; mp 118-121°C
1
(o-xylene). IR spectrum (CHCl3), ν, cm-1: 1600 and 1523 (NCO), 1580 (Ar). H NMR spectrum (CDCl3),
δ, ppm: 0.39 (6H, s, OSiMe2); 0.68 (6H, s, SiMe2Cl); 3.00 (2H, s, CH2SiCl); 3.10 (2H, s, NCH2SiO); 7.12, 7.44,
6.95, 7.49 (4H, t, dt, ddd, C6H4). Found, %: C 49.70; H 6.31; Si 17.77. C13H20ClNO2Si2. Calculated, %: C 49.72;
H 6.42; Si 17.89.
The crystals for the X-ray diffraction structural analysis were prepared by recrystallizing 4 from
p-xylene.
B. A sample of thionyl chloride (1.2 g, 0.01 mol) was added dropwise with stirring to a mixture of
compound 5 and o-xylene (10 ml). After 24 h, the precipitate formed was filtered off to give 3.0 g (95%) of
compound 4; mp 121-124°C (p-xylene). IR spectrum (CHCl3), ν, cm-1: 1600 and 1525 (NCO), 1580 (Ar).
Hydrolysis of 2,2,4-trimethyl-1-oxa-4-aza-2-sila-5-benzocycloheptanone (1). A. A solution of
silacyclane 1 (5 g, 0.023 g) in chloroform (10 ml) with aqueous sodium bicarbonate (5 ml) was heated at reflux
for 5 h. The organic layer was separated. Chloroform was removed and the residue was fractionated in vacuum
to give 4.8 g (96%) of starting 1; bp 180-182°C (8 mm Hg).
B. A sample of silacyclane 1 (2.5 g, 0.011 mol) was dissolved in 10% aq. KOH (15 ml) with moderate
heating. The solution obtained was acidified by adding 0.01 mol/liter sulfuric acid to pH 6. The crystalline
residue obtained after 24 h was filtered off to give 1.8 g (72%) of 1,1,2,2-tetramethyl-1,2-bis[(N-methyl-2-
hydroxybenzoylamino)methyl]-1,2-disiloxane (3); mp 108-109°C. IR spectrum (CHCl3), ν, cm-1: 1597 (NCO).
1H NMR spectrum (CDCl3), δ, ppm: 0.04 (6H, s, 2SiMe2); 3.15 (2H, s, NCH2Si); 3.31 (6H, s, 2NMe); 6.42-7.34
(4H, m, C6H4); 9.16 (2H, s, 2OH). Found, %: C 58.30; H 7.43. C22H32N2O5Si2. Calculated, %: C 57.36; H 7.00.
C. A sample of water (3 ml, 0.16 mol) was added to a solution of silacyclane 1 (2.5 g, 0.011 mol) in
acetonitrile (8 ml). The reaction mixture was heated at reflux with vigorous stirring. The solution was cooled
and the precipitate formed was filtered off and recrystallized from 1:1 acetonitrile–water to give 2.0 g (77%) of
1,1,2,2-tetramethyl-1,2-bis[(N-methyl-2-hydroxybenzoylamino)methyl]-1,2-disiloxane (3); mp 106-108°C.
IR spectrum (CHCl3), ν, cm-1: 1597 (NCO).
2,2,6,6-Tetramethyl-4-(2-hydroxybenzoyl)-2,6-disilamorpholine (5). A. A solution of compound 4
(21 g, 0.067 mol) in chloroform (100 ml) was stirred for 2 h with a solution of NaHCO3 (5.6 g) in water (50 ml).
The organic layer was separated and the aqueous layer was extracted with chloroform (50 ml). The organic
layers were combined and the solvent was removed. The residue was crystallized from toluene (40 ml). The
crystalline precipitate formed was separated to give 17.8 g (90%) of compound 5; mp 150-152°C (toluene).
1
IR spectrum (CHCl3), ν, cm-1: 1637 (NCO), 1600, 1590 (Ar). H NMR spectrum (CDCl3), δ, ppm, J (Hz): 0.22
3
1
3
(6H, s, 2SiMe2); 3.20 (4H, s, 2CH2); 6.99 (1H, d, JHH = 8.3); 6.83 (1H, t, JHH = 8.3); 7.27 (1H, t, JHH = 8.3);
3
7.31 (1H, t, JHH = 8.3, Ar); 9.38 (1H, s, OH). Found, %: C 52.79; H 7.14. C13H21NO3Si2. Calculated, %:
C 52.84; H 7.16.
The crystals of 5 for the X-ray diffraction analysis were obtained from toluene.
B. A sample of dimethylchloromethylchlorosilane (35.5 g, 0.25 mol) was added with stirring to a
mixture of salicylamide (6.85 g, 0.05 mol), hexamethyldisilazane (20.1 g, 0.125 mol), and toluene (50 ml) and
heated at reflux for 8 h. The mixture was filtered and the solvent evaporated. The residue was dissolved in
chloroform (50 ml) and stirred with a solution of NaHCO3 (4.2 g) in water (30 ml) for 2 h. The organic layer
125

was separated and the aqueous layer was extracted with chloroform (30 ml). The solvent was removed from the
combined organic layers and the residue was crystallized from toluene (30 ml) to give 10.9 g (74%) of
compound 5; mp 150-152°C (toluene). IR spectrum (CHCl3), ν, cm-1: 1637 (NCO), 1600, 1590 (Ar).
2,2,6,6-Tetramethyl-4-(2-hydroxybenzoyl)-2,6-disilamorpholine Hydrochloride (5·HCl). A sample
of chloride 4 was stored under conditions excluding atmospheric moisture for six months. The mp changed from
118-121°C (p-xylene) to 146-150°C. This product was 5·HCl. IR spectrum taken on a Specord M82
spectrometer with CaF2 plates in vaseline mull, ν, cm-1: 1735, 1640 (NCO), 1606, 1573 (Ar). Found, %:
C 47.02; H 6.68; N 4.22. C13H22ClNO3Si2. Calculated, % C 47.04; H 6.68; N 4.22.
The crystals of hydrochloride 5·HCl for the X-ray diffraction analysis were obtained from benzene.
2,2-Dimethyl-4-(dimethylfluorosilylmethyl)-1-oxa-4-aza-2-sila-5-benzocycloheptanone
(6).
A
mixture of hexamethyldisilazane (1.55 g, 9.6 mmol), methanol (0.31 g, 9.6 mmol), and benzene (10 ml) was
added with stirring to a cooled mixture of chloride 4 (1.5 g, 4.8 mmol) and benzene (10 ml). After 24 h, the
precipitate of NH4Cl was filtered off and the reaction mixture was dissolved in benzene (10 ml). Then, BF3·Et2O
(0.23 g, 1.6 mmol) was added dropwise with cooling. After 24 h, the reaction mixture was evaporated and
diethyl ether (10 ml) was added. The precipitate (0.25 g) was separated. Ether was removed and the residue was
recrystallized by adding heptane (10 ml) to give 0.75 g (52%) of compound 6; mp 102-105°C (ether).
1
IR spectrum (CHCl3), ν, cm-1: 1620, 1578 (NCO), 1600 (Ar). H NMR spectrum (CDCl3), δ, ppm, J (Hz): 0.38
3
(6H, s, SiMe2); 0.39 (6H, s, SiMe2); 2.73 (2H, s, CH2); 2.95 (2H, s, CH2); 6.93 (1H, d, JHH = 8.3); 7.39 (1H, t,
3
3
3JHH = 8.3); 7.10 (1H, t, JHH = 8.3); 7.51 (1H, d, JHH = 8.3, Ar). Found, %: C 51.98; H 6.94; N 4.21.
C17H20FNO2Si2. Calculated, %: C 52.49; H 6.78; N 4.71.
Crystals of 6 for the X-ray diffraction analysis were obtained from ether.
X-ray Crystallography. The crystal structure parameters and major features of the X-ray diffraction
experiments for 4, 5, 5·HCl, and 6 are given in Table 2. The experiments were carried out on Syntex P21 (4 and
HCl) using λMoK
6), Siemens P3/PC (5), and SMART CCD diffractometers (5·
α radiation and graphite
monochromator. The structures were solved by the direct method and refined by the method of least squares
relative to F2 anisotropically for the nonhydrogen atoms. The hydrogen atoms in the structures of 4, 5·HCl, and
6 were revealed in the difference map and refined isotropically. The hydrogen atoms in the structure of 5 were
placed in calculated positions and refined by the rider model with fixed temperature parameters U equal to
1.2Uc for the CH2 group and 1.5Uc for the methyl groups (Uc is the equivalent temperature parameter of the
corresponding carbon atom). A profile analysis was carried out for the reflection data obtained from a crystal of
6 using the PROFIT program [19]. All the calculations were carried out on an IBM PC using the SHELXTL
PLUS program package (version 5.0) [20]. The atomic coordinates for these structures have been deposited in
the Cambridge Structural Data Bank. The major bond lengths and angles are given in Tables 3-6.
The authors are grateful to the Russian Basic Research Fund (Projects No. 98-03-32999 and
97-03-33783) and the GK RF po VO (General and Technical Chemistry P.T.402.95, Project No. 01.0204f) for
financial support of this work.
REFERENCES
1.
2.
3.
Yu. I. Baukov, A. G. Shipov, E. P. Kramarova, E. A. Mamaeva, O. A. Zamyshlyaeva, N. A. Anisimova,
and V. V. Negrebetsky, Zh. Org. Khim., 32, 1259 (1996).
E. A. Mamaeva, O. V. Agafonova, V. V. Negrebetsky, A. G. Shipov, Yu. I. Baukov, and A. S. Losev,
Khim.-Farm. Zh., No. 6, 26 (1994).
A. V. Kurochka, O. A. Afanasova, A. S. Losev, E. A. Mamaeva, S. Yu. Bylikin, V. V. Negrebetsky,
E. P. Kramarova, A. G. Shipov, and Yu. I. Baukov, Metal-Based Drugs, 5, 25 (1998).
126

4.
5.
E. P. Kramarova, V. V. Negrebetsky, A. G. Shipov, and Yu. I. Baukov, Zh. Obshch. Khim., 64, 1222
(1994).
O. A. Zamyshlyaeva, A. G. Shipov, E. P. Kramarova, V. V. Negrebetsky, Yu. E. Ovchinnikov,
S. A. Pogozhikh, and Yu. I. Baukov, Khim. Geterotsikl. Soedin., 1077 (1999).
C. Chuit, R. J. P. Corriu, C. Reye, and J. C. Yuong, Chem. Rev., 93, 1371 (1993).
A. G. Shipov, E. P. Kramarova, S. Yu. Bylikin, E. A. Mamaeva, G. S. Zaitseva, V. N. Sergeev, and
Yu. I. Baukov, Zh. Obshch. Khim., 63, 1195 (1993).
6.
7.
8.
9.
10.
I. D. Kostas, C. G. Screttas, C. P. Raptopoulou, and A. Terzis, Tetrahedron Lett., 38, 8761 (1997).
A. G. Shipov, E. P. Kramarova, and Yu. I. Baukov, Zh. Obshch. Khim., 64, 1220 (1994).
V. M. D'yakov and G. I. Orlov, Medium-Size Nitrogen Silacyclanes [in Russian], NIITEKhIM, Moscow
(1985), p. 11.
11.
12.
M. G. Voronkov, V. A. Pestunovich, and Yu. I. Baukov, Metalloorg. Khim., 4, 1210 (1991).
G. Emsley, J. Finney, and L. Sutcliffe, High-Resolution NMR Spectroscopy [Russian translation],
Vol. 1, Mir, Moscow (1968).
13.
A. G. Shipov, E. P. Kramarova, E. A. Mamaeva, O. A. Zamyshlyaeva, V. V. Negrebetsky,
Yu. E. Ovchinnikov, S. A. Pogozhikh, A. R. Bassindale, P. G. Taylor, and Yu. I. Baukov,
J. Organometall. Chem. (in press).
14.
15.
V. V. Negrebetsky and Yu. I. Baukov, Izv. Akad. Nauk, Ser. Khim., 1912 (1997).
V. V. Negrebetsky, E. P. Kramarova, A. G. Shipov, and Yu. I. Baukov, Zh. Obshch. Khim., 67, 1304
(1997).
16.
V. V. Negrebetsky, A. G. Shipov, E. P. Kramarova, V. V. Negrebetsky, and Yu. I. Baukov,
J. Organometall. Chem., 530, 1 (1997).
17.
18.
A. Bondi, J. Phys. Chem., 68, 441 (1964).
Yu. E. Ovchinnikov, A. A. Macharashvili, Yu. T. Struchkov, A. G. Shipov, and Yu. I. Baukov,
Zh. Strukt. Khim., 35, 100 (1994).
19.
20.
V. E. Strel'tsov and V. E. Zavodnik, Kristallografiya, 34, 1369 (1989) [Sov. Phys. Crystallogr. (1989)
(Engl. Transl.)].
G. M. Sheldrick, SHELTXTL PC Version 5.0, An Integrated System for Solving, Refining, and
Displaying Crystal Structures from Diffraction Data, Siemens Analytical X-ray Instruments, Madison,
WI (1994).
127