Silylated derivatives of N-(2-hydroxyphenyl)acetamide: Synthesis and structure

Article abstract of DOI:10.1016/j.molstruc.2016.05.072

The N-(2-(trimethylsilyloxy)phenyl)acetamide 1 was synthesized via reaction of N-(2-hydroxyphenyl)acetamide with chlorotrimethylsilane. Transsilylation of new compound 1 by chloro(chloromethyl)dimethylsilane leads to 4-acetyl-2,2-dimethyl-3,4-dihydro-2H-1,4,2-benzoxazasiline 3. The structures of the new compounds were investigated by ¹H, ¹³C and ²⁹Si NMR spectroscopy, X-ray single-crystal analysis, FTIR spectroscopy and DFT methods.

Full text of DOI:10.1016/j.molstruc.2016.05.072

Accepted Manuscript
Silylated derivatives OF N-(2-hydroxyphenyl)acetamide: Synthesis and structure
Alexey Yu Nikonov, Irina V. Sterkhova, Igor M. Lazarev, Alexander I. Albanov,
Natalya F. Lazareva
PII:
S0022-2860(16)30521-X
10.1016/j.molstruc.2016.05.072
MOLSTR 22586
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 6 April 2016
Revised Date: 18 May 2016
Accepted Date: 20 May 2016
Please cite this article as: A.Y. Nikonov, I.V. Sterkhova, I.M. Lazarev, A.I. Albanov, N.F. Lazareva,
Silylated derivatives OF N-(2-hydroxyphenyl)acetamide: Synthesis and structure, Journal of Molecular
Structure (2016), doi: 10.1016/j.molstruc.2016.05.072.
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ACCEPTED MANUSCRIPT
SILYLATED DERIVATIVES OF N-(2-HYDROXYPHENYL)ACETAMIDE: SYNTHESIS
AND STRUCTURE
Alexey Yu. Nikonov, Irina V. Sterkhova, Igor M. Lazarev, Alexander I. Albanov, Natalya F.
Lazareva*
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of
Sciences,1 Favorskogo st. 664033, Irkutsk, Russia, Correspondence e-mail:
nataly_lazareva@irioch.irk.ru
Abstract
The N-(2-(trimethylsilyloxy)phenyl)acetamide 1 was synthesized via reaction of N-(2-
hydroxyphenyl)acetamide with chlorotrimethylsilane. Transsilylation of new compound 1 by
chloro(chloromethyl)dimethylsilane leads to 4-acetyl-2,2-dimethyl-3,4-dihydro-2H-1,4,2-
1
13
29
benzoxazasiline 3. The structures of the new compounds were investigated by H, C and Si
NMR spectroscopy, X-ray single-crystal analysis, FTIR spectroscopy and DFT methods.
Key words: N-(2-hydroxyphenyl)acetamide, N-(2-(trimethylsilyloxy)phenyl)acetamide, N-[2-
(trimethylsilyloxy)pheny])-N-trimethylsilylacetamide,
1,4,2-benzoxazasiline
4-acetyl-2,2-dimethyl-3,4-dihydro-2H-
1. Introduction
N-(4-Hydroxyphenyl)acetamide, also known as paracetamol or acetaminophen or APAP
is a popular medication with analgesic and antipyretic effect and numerous publications have
been devoted to the study of its properties. It is the important medication needed in a basic health
system [1, 2]. Its structural isomer - N-(2-hydroxyphenyl)acetamide is less known compound
and its properties have been little studied. According to NMR data, molecule of N-(2-
hydroxyphenyl)acetamide in solution (CDCl3, DMSO-d6) exists in the form of its conformer
with intramolecular hydrogen bond C=O…HO bonds between the hydroxy and carbonyl groups
of adjacent molecules [3]. Methods of synthesis and chemical properties of this compound have
been examined intensively in recent years [see example 4-18]. Increased interest in the study of
the properties of N-(2-hydroxyphenyl)acetamide may be due to the fact that it is potentially
suitability for use in medicine. Recent investigation showed that this compound prominently
suppresses inflammation and it is very good candidate for the prevention of cardiovascular
diseases and rheumatoid arthritis [19-23]. Notice that it is a less toxic compound compared to

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paracetamol or aspirin and can be used as an anti-inflammatory and antiplatelet aggregating
agent [23]. This amide possesses strong apoptotic activity on U87 GBM cells [24]. Recently the
antitubercular activity of N-(2-hydroxyphenyl)acetamide was investigated and was found an
minimum inhibitory concentration value of 132 µM against Mycobacterium tuberculosis H37Rv
and a selectivity index value of 32 [25].
It is common knowledge that O- and N-silylation of organic compounds is an important
tool in gas chromatography, mass spectrometry and synthetic chemistry for the derivatisation of
a wide variety of products and functional groups. Silylation of functional groups results in
reduced polarity, enhanced volatility and increased chemical and thermal stability of compounds
[see example 26-29 and references therein]. Any data about O- or N-silylated derivatives of N-
(2-hydroxyphenyl)acetamide is absent in the literature. There is no information about a N-
(silylmethyl)derivatives of this amide. N-(Silylmethyl)carboxamides exhibit a wide range of
biological activity. They are inhibitors of enzymes [30-32], suppress cell growth of human
pancreatic carcinoma [33]. N-(Silylmethyl)amides of N-acetyl-L-cysteine are stronger
antioxidants than N-acetyl-L-cysteine due to an increase in lipophilicity of the molecules and, as
a consequence, their bioaccessibility [34, 35]. Six- and seven-membered 4-aza-1-oxa-2-
silacyclanes can find an use as correctors of adaptation mechanisms [36-38]. On basis aforesaid
about biological activity of N-(2-hydroxyphenyl)acetamide can be expected that N-
silylmethylation of N-(2-hydroxyphenyl)acetamide may give rise to the preparation of new
effective drugs. The aim of this work is to obtain a Si-containing derivatives N-(2-
hydroxyphenyl)acetamide and study of their structure.
2. Experimental section
2.1. Synthesis and crystallization
All reactions were performed in the flame dried glassware under an atmosphere of dry
argon. The used solvents were purified according to standard procedures [39]. The solvents were
stored under argon over molecular sieves. Commercial trimethylchlorosilane and
(chloromethyl)dimethylchlorosilane were distilled in the presence of Bu3N directly before use.
Triethylamine was dried by distillation over CaH2.
IMPORTANT! Compound 2 is extremely sensitive to moisture. We have failed and have not
allocated the pure compound. We have given only its spectral characteristics.
2.2. N-(2-(trimethylsilyloxy)phenyl)acetamide (1).

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a) The mixture of N-(2-hydroxyphenyl)acetamide (5.6 g, 37 mmol) and the excess of
hexamethyldisilazane (6.5 g, 40 mmol) was refluxed for 24 h . The solid was washed with
hexane (2x50 ml) and dried in vacuo to give threadlike colorless crystals (7.4 g, 90%).
b) Chlorotrimethylsilane (8.7 g, 80 mmol) in 30 ml of benzene was added dropwise under
vigorous stirring to a suspension of N-(2-hydroxyphenyl)acetamide (6 g, 40 mmol) in 120 ml of
benzene with 9 ml of triethylamine. The reaction mixture was stirred for 6 h at 60° C and a
precipitate of Et3N•HCl was filtered off. The solvent was evaporated in vacuo and the residue
was washed with hexane (2x50 ml). The resulting solid was dried in a vacuo to give white
crystals (7.6 g, 45%). Recrystallization from acetonitrile gave colorless single crystals suitable
for X-ray crystallography. Mp: 370° K. IR (KBr, cm-1): 771, 847, (νSi-C), 1109 (νSi-O), 1250
1
(νC-N), 1275, 1454, 1488, 1533 (δC-H), 1633 (νC=O), 2961, 3196 (νC-H), 3292 (νNH). H
NMR (CDCl3, δ, ppm): 0.32 (s, 9H, (CH3)3Si), 2.17 (s, 3H, CH3C=O), 6.80 (m, 1H, 3-H), 6.94
(m, 2H, 4,5-H), 7.61 (s, 1H, NH), 8.30 (m, 1H, H-6). 13C NMR (CDCl3, δ, ppm): 0.34
((CH3)3Si), 25.0 (CH3C=O), 117.8 (C3), 120.5 (C6), 122 (C5), 123.7 (C4), 129.9 (C1), 143.9 (C2),
168.0 (C=O). 29Si NMR (CDCl3, δ, ppm): 21.8. Anal. calcd. for C11H17NO2Si: C, 59.15; H, 7.67;
N, 6.27; Si, 12.58. Found: C, 58.77; H, 7.60; N, 7.06; Si, 12.33.
2.3. N-[2-(trimethylsilyloxy)pheny])-N-trimethylsilylacetamide (2)
N-[2-(trimethylsilyloxy)phenyl]-N-trimethylsilylacetamide is generated as subproduct in
reaction of N-(2-hydroxyphenyl)acetamide with Me3SiCl in presence of triethylamine. The ratio
1
1
of 1:2 in reaction mixture is about 1 : 0.8 (accordingly to NMR H data). H NMR (CDCl3, δ,
ppm): 0.08 (s, 9H, (CH3)3Si-O), 0.22 (s, 9H, (CH3)3Si-N), 1.75 (s, 3H, CH3C=O), 6.78 – 7.2 (m,
13
4H, Ph). C NMR (CDCl3, δ, ppm): -0.18 ((CH3)3Si-O), 0.54 ((CH3)3Si-N), 23.00 (CH3C=O),
29
118.8 (C3), 121.4 (C6), 128.2 (C5), 129.8 (C4), 130.4 (C1), 152 (C2), 168.0 (C=O). Si NMR
(CDCl3, δ, ppm): 9.01(NSiMe3), 19.1(OSiMe3).
2.4. 4-acetyl-2,2-dimethyl-3,4-dihydro-2H-1,4,2-benzoxazasiline (3)
a) Chloro(chlotomethyl)dimethylsilane (5 g, 35 mmol) in 30 ml of benzene was added dropwise
under stirring to a suspension of N-(2-hydroxyphenyl)acetamide (5.3 g, 35 mmol) in 110 ml of
benzene with 7.2 ml of triethylamine. The reaction mixture was stirred for 6 h at 60° C then a
precipitate of Et3N•HCl was filtered off and washed with 30 ml of benzene. The solvent was
evaporated in vacuo. Vacuum distillation gave colorless liquid (bp = 133-137° C at 3 torr). After
1 month storage in a sealed flask the liquid changed its color to black and the colorless crystals

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were found at the flask bottom. The crystals were washed with 5 ml of hexane and dried in a
vacuo (1.47 g, 19%).
b) The mixture of N-[2-(trimethylsilyloxy)phenyl]acetamide 1 (2.9 g, 13 mmol) and
triethylamine (1.5 g, 15 mmol) in 50 ml of benzene was treated dropwise under stirring with
mixture of chloro(chloromethyl)dimethylsilane (1.86 g, 13 mmol) in 10 ml of benzene. After
stirring of the reaction mixture at room temperature for 40 h and filtration the solvent was
evaporated. The residue was sublimated in vacuum (t = 118°C, 2 torr) to give colorless crystals
(2.16 g, 75%). Mp: 357° K. IR (KBr, cm-1): 751, 838 (νSi-C), 1084 (νSi-O), 1247 (νC-N), 1274,
1
1390, 1489 (δC-H), 1651 (νC=O), 2911, 2963 (νC-H). H NMR (CDCl3, δ, ppm): 0.34 (s, 6H,
3
(CH3)2Si), 2.11 (s, 3H, CH3C=O), 3.43 (broad. s, 2H, CH2), 6.92 (d.d., 1Н, Н-6, 3J = 7.9 Hz; J = 7.6
Hz); 6.95 (d., 1Н, Н-8, 3J = 7.6 Hz); 7.07 (d., 1Н, Н-5, 3J = 7.9 Hz); 7.16 (tr.d., 1Н, Н-7, 3J7-6= 3J7-8=
4
7.6 Hz; J7-5 = 1.2 Hz); 13C NMR (CDCl3, δ, ppm): -1.3 ((CH3)2Si), 22.0 (CH3C=O), 33.6 (CH2),
29
120.2 (C8), 121.0 (C6), 126.6 (C5), 127.9 (C7), 131.8 (C4a), 149.8 (C8a), 169.1 (C=O). Si NMR
(CDCl3, δ, ppm): 21.7. Anal. calcd. for C11H15NO2Si: C, 59.69; H, 6.83; N, 6.33; Si, 12.69.
Found: C, 58.55; H, 6.98; N, 6.24; Si, 12.25.
2.5. X-ray study and refinement
Crystal data were collected on a Bruker D8 Venture diffractometer with MoKa radiation
(λ = 0.71073) using the φ and ω scans. The structures were solved and refined by direct methods
using the SHELX programs set [40]. Data were corrected for absorption effects using the multi-
scan method (SADABS). Nonhydrogen atoms were refined anisotropically using SHELX [40]
(Sheldrick, 2008). Crystal data, data collection and structure refinement details are summarized
in Table 1. CCDC 1436048 (compound 1) and CCDC 1412270 (compound 3) contain the
supplementary crystallographic data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
2.6. Quantum chemical calculations
All calculations were performed using the Gaussian 09 suite of programs [41] with full
optimization of all variables without any symmetry restrictions imposed on the initial structures.
DFT calculations with 6-311+G** basis set were used for the monomer and dimer of compound
1. All calculated structures correspond to minima on the potential energy surface (PES) as
proved by positive eigenvalues of the corresponding Hessian matrices. All energies were
calculated with the ZPE correction.
2.7. NMR spectroscopy

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1
The H, 13C and 29Si NMR spectra of 10-20% solutions of compounds 1-3 were
registered on a Bruker DPX 400 spectrometer (400.1, 100.6 and 79.5 MHz respectively) with
tetramethylsilane or cyclohexane as an internal standard.
2.8. IR spectroscopy
The FT-IR spectra were taken on an FT-IR Spectrometer Varian 3100. For neutral
compounds the spectra were recorded in KBr pellets. The spectra of the H-bonded self-associates
of compound 1 were registered in CCl4 solution with different concentration (0.02 mol/l - 0.1
mol/ l).
3. Results and discussion
3.1. Synthesis
The interaction of N-(2-hydroxyphenyl)acetamide with hexamethyldisilazane (HMDS)
lead to the formation of O-trimethylsilyl derivative - N-(2-(trimethylsilyloxy)phenyl)acetamide
1 with good yield (90%) (Scheme 1). The reaction runs at the reflux of reaction mix for 24 h.
Reflux of N-(2-hydroxyphenyl)acetamide with twofold excess of HMDS didn’t led to silylation
of NH group.
Scheme 1.
N-(2-Hydroxyphenyl)acetamide interacts with two equivalents of Me3SiCl in presence of
triethylamine as hydrogen chloride acceptor with forming of mixture of compound 1 and N-[2-
(trimethylsilyloxy)pheny])-N-trimethylsilylacetamide 2 with ratio 1 : 2 = 1 : 0.8 (Scheme 2).
Unfortunately we failed the isolation of compound 2 due to its low hydrolytic stability, high
boiling temperature and major impurity of 1 complicating the distillation of desirable compound
2.

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Scheme 2.
The reaction of compound 1 with ClCH2SiMe2Cl in presence of triethylamine leads to
formation of 6-membered heterocyclic compound - 4-acetyl-2,2-dimethyl-3,4-dihydro-2H-1,4,2-
benzoxazasiline 3 represented as colorless crystals (Scheme 3).
O
C
O
C
Me
NH
Me
N
SiMe2
O
Et3N
- Et3N . HCl
O
+
ClCH2SiMe2Cl
SiMe3
1
3
Scheme 3.
Based on an analysis of published data about the study of the mechanism of interaction
of ClCH2SiMe2Cl with a carboxamides [42-44], we suggest the following possible mechanism
for the formation of compound 3 from amide 1 (Scheme 4). Apparently, under these conditions
the formation of unstable product A was observed at the first stage of the reaction. The similar
intermediates were identified at low temperature by monitoring of NMR spectroscopy [42]. This
intermediate was completely converted by a tautomerization to B or by an internal alkylation to
C. The formation of (O-Si) chelate compound D with pentacoordinate silicon atom may result
either from the Chapman-like rearrangement of intermediate C or by N-alkylation of the O-
silylated intermediate B with the followed migration of chloride to silicon atom. An enhanced
reactivity of Si–Cl bond is typical for hypervalent silicon compounds [45] and intramolecular
cyclisation of (O-Si) chelate compound D lead to formation of heterocyle 3.
heterocyclisation was observed at interaction of ClCH2SiMe2Cl
trimethylsilylcarboxamides containing the hydroxyl group at the acid rest [46, 37].
A
related
with N-

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O
OSiMe2CH2Cl
C
SiMe2CH2Cl
OSiMe3
ClCH2SiMe2Cl,
Et3N
- Et3N . HCl
C
N
Me
N
Me
1
OSiMe3
A
B
Me
N
Me
O
C
Cl
O
C
Si Cl
Si
Me
Me
Me
N
Me
OSiMe3
OSiMe3
C
D
- Me3SiCl
3
Scheme 4.
Direct silylation of N-(2-hydroxyphenyl)acetamide by ClCH2SiMe2Cl by using triethylamine as
hydrogen chloride acceptor followed by distillation giving colorless liquid rapidly turned
magenta on air exposure. According to data of NMR spectra this liquid is mixture of heterocycle
3 (~35%), 2-methylbenzoxazole (~38%) and 1,3-bis(chloromethyl)-1,1,3,3-tetramethyldisiloxane
(~27%) (Scheme 5). The presence of 2-methylbenzoxazole can be explained by transformation
of unreacted N-(2-hydroxyphenyl)acetamide under the heating of the reaction mixture. It is
known that N-(2-hydroxyphenyl)acetamide under acidic conditions forms 2-methylbenzoxazole
[11, 17]. Acid was probably generated by partial hydrolysis of initial ClCH2SiMe2Cl by air
moisture or trace amounts of water, adsorbed on N-(2-hydroxyphenyl)acetamide. The stored
product in a sealed ampule for two months gradually changing its color from slightly pink to
dark maroon. Flat crystals of heterocycle 3 were found at the bottom of ampule. It should be
noted that compound 3 is quite stable since its NMR spectra obtained after a 10 months storing at
sealed ampule are the same as initial spectra.

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O
C
O
C
N
O
Me
NH
Me
N
ClCH2SiMe2Cl,
Et3N, benzene
- Et3N . HCl
SiMe2
O
Me
+
OH
3
+ (ClCH2SiMe2)2O
Scheme 5.
3.2. NMR
NMR chemical shifts for Si-methyl groups of products are similar to those for 2,2,4-Trimethyl-1-
oxa-4-aza-2-sila-[6,7]-benzocycloheptan-5-one described in [37] . The values of chemical shifts
for methylene group protons of silacyclane 3 and Si-containing derivative of salicylamide are
1
3.43 ppm and 2.89 ppm respectively. However, H NMR spectrum of compound 3 is quite
different from spectrum of 2,2,4-trimethylsilyl-1-oxa-4-aza-2-silabenzocycloheptan-5-on. The
key difference is an extreme broadening of methylene protons chemical shift in compound 3,
explained by rotation of acetyl moiety about C-N bond and considerable influence of carbonyl
group anisotropy. The structure of salicylamide cyclic derivative in [37] is rigid and excludes
rotation, thus the broadening of peaks is not observed. Variable temperature NMR experiment
proved this assumption and allowed to determine average chemical shift for two possible
rotamers of compound 3 (Fig.1). Probably, the reason of the extreme broadening of resonances
Fig.1. Fragment of 1H NMR spectra of 3 at 295° K (a) and 325° K (b).
methylene protons of compound 3 is a result of the superposition of two processes: a
conformational isomerism of heterocycle and the hindered rotation of this heterocycle around

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the amide bond C-N. It should be noted that the broadening of signal of methylene protons of
heterocycles is the case in the NMR 1H spectrum of structurally related N-acylindolines [47].
29Si NMR chemical shifts for new compounds 1-3 are located in 9 to 22 ppm range characteristic
for NSiMe3- and OSiMe3(2) – groups, respectively, of tetracoordinate silicon compounds.
3.3. Structural analysis
The X-ray single-crystal structure of amides 1 and 3 has been determined (Fig. 2). Crystal
data, data collection and structure refinement details are summarized in Table 1. Principal bond
distances, bond angles and torsion angles are presented in Table 2.
Table1. Experimental data and precise structures of compounds 1 and 3.
Amide
1
3
Formula
Specimen
C11H17NO2Si
colorless plate
C11H15NO2Si
colorless prism
0.460 x 0.500 x 0.500
1412270
Spice dimensions, mm 0.080 x 0.250 x 0.500
CCDC
№
1436048
100
Temperature,
К
100
Crystal system
Space group
Mr, g/mol
orthorhombic
P b c a
Monoclinic
P1 21/c
223.34
221.33
θmin
/
θmax
,
2.47 / 30.08
3.05 / 30.09
14.0116(13)
6.9391(6)
13.3575(11)
117.749(3)
a, Å
b, Å
c, Å
9.1794(9)
15.9177(14)
16.5166(16)
90
β
, ˚
V, Å3
Z
2413.3(4)
1149.36(18)
4
8
Dcalc, g/cm3
1.229
960
1.279
472
F (000)
Absorp. Coeff., mm-1
0.176
67276
0.185
46115
3367
139
Reflections collected
Independent reflections 3541
Number of ref.param.
Final R1 , %
140
3.73
3.41
Rw (all data)
0.0507
0.0393

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Goodness-of-fit on F2
∆ρ and ∆ρ)min,
1.098
1.061
0.409 and -0.429
0.370 and -0.344
(
)
max
(
e/Å3
2
2
w=1/[σ2(Fo )+(0.0449P)2+1.1507 w=1/[σ2(Fo )+(0.0491P)2+0.4845
Weight scheme
P]
where P=(Fo +2Fc2)/3
P]
where P=(Fo +2Fc2)/3
2
2
Table 2. Selected bond lengths, bond and torsion angles in compounds 1 and 3.
Amide Bond
Si1-O1
l
, Å
Angle
φ
, ˚
Angle
θ, ˚
1.6772(9)
O1-Si1-C6 104.42(5)
C6-Si1-O1-C4
N1-C3-C4-O1
N1-C3-C8-C9
C7-Si1-O1-C4
-174.56(9)
3.48(15)
1
Si1-C7
O1-C4
N1-C2
C3-C4
Si1-C6
O2-C2
N1-C3
Si1-O1
Si1-C1
O1-C2
N1-C8
N1-C7
Si1-C6
Si1-C7
O2-C8
1.8557(13) C6-Si1-C7 111.93(6)
1.3742(13) C6-Si1-C5 111.38(6)
1.3548(14) C4-O1-Si1 122.84(7)
174.15(11)
66.09(9)
1.4007(16) O2-C2-N1
1.8490(13) N1-C2-C1
1.2324(14) C8-C3-N1
123.69(10) C3-N1-C2-O2
114.89(10) C2-N1-C3-C8
7.72(18)
37.29(17)
122.49(10) Si1-O1-C4-C11 -86.78(12)
1.4170(14) O1-Si1-C7 108.16(5)
1.6871(8) O1-Si1-C6 108.43(5)
C8-C3-C4-O1
C6-Si1-O1-C2
C7-Si1-O1-C2
179.66(10)
-118.71(9)
1.68(9)
3
1.8468(12) C6-Si1-C1 113.36(6)
1.3609(12) C6-Si1-C7 114.18(5)
1.3690(13) C2-O1-Si1 124.66(7)
Si1-O1-C2-C10 -25.21(13)
C10-N1-C7-Si1 -65.74(9)
1.4832(12) C8-N1-C7
119.39(8)
C6-Si1-C7-N1
C1-Si1-O1-C2
Si1-O1-C2-C3
O1-C2-C3-C4
C1-Si1-C7-N1
155.46(7)
119.22(9)
154.72(8)
179.96(9)
-73.54(8)
1.8442(11) C10-N1-C7 114.68(8)
1.8739(10) O1-Si1-C1 106.07(5)
1.2299(12) O1-Si1-C7 101.17(4)
N1-C10 1.4280(12) C8-N1-C10 125.41(8)
Silicon atom is tetracoordinated in both structures 1 and 3. The geometry of SiMe3 group in
compound 1 is near to such in known structures [48, 49], C-Si-C angles are 111.1-111.9º, C-Si-O
angles are 104.4-109.5º. In compound 3 C-Si-C and C-Si-O angles consist 112.4-114.1º and
101.1-108.5º accordingly, that very close to the geometry of 2,2-dimethyl-1,2,4-oxazasilinane
fragment
in
(3,3,7,7-tetramethyltetrahydro-1H-[1,4,2]oxazasilino[4,5-d][1,4,2]oxazasilin-
9a(9H)-yl)methanol [50].

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According to X-ray data molecules of compound 1 present in trans-form of amide moiety (Fig.
2, left) that is general for most amides and in particular for recently investigated N-
(trimethylsilyl)amides [51]. Only two similar structures having {[(trimethylsilyl)oxy]phenyl}-
amide fragment were found for compound 1 [52]. {[(Trimethylsilyl)oxy]phenyl}acetamide 1 has
torsion angles N1-C3-C4-O1 equal 3.52o that very close to such for 3,5-dimethyl-N-(2-
((trimethylsilyl)oxy)phenyl)-1H-pyrazole-1-carboxamide
(3.45o)
and
2-oxo-N-(2-
((trimethylsilyl)oxy)phenyl)-1,3-benzoxazole-3(2H)-carboxamide (1.50o) [52]. So N and O
atoms lie near the plane of benzene ring for all these structures. Angles of deviation of Me3Si
group (Si atom) from plane of benzene ring are also near and consist 122.84˚ for compound 1
and about 127-128˚ for other two structures [52]. However, the structure of compound 1 has
differences from structures what were studied in [52]. Whereas O=C-N-H fragment in 3,5-
dimethyl-N-(2-((trimethylsilyl)oxy)phenyl)-1H-pyrazole-1-carboxamide
and
2-oxo-N-(2-
((trimethylsilyl)oxy)phenyl)-1,3-benzoxazole-3(2H)-carboxamide is in plane of benzene ring,
angles of deviation consists 2.65˚ and 1.21˚ respectively, in compound 1 the angle is 41.07˚.
Very likely such behavior connects with formation of hydrogen bonding chains in structure of
compound 1 (Fig.3). The distance NH···OC is 2.111 Å.
Fig. 2. Molecular structures of compounds 1 and 3.

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Fig. 3. Fragment of chain structure of compound 1.
Unfortunately, we didn’t find structural analogues in CCDC for bicyclic compound 3
(Fig. 2 right). In literature there are just one structure with bicyclic 2,2-dimethyl-1,2,3,4-
tetrahydro-2-benzazasiline fragment [53] and several structures with 2,2-dimethyl-1,2,3,4-
tetrahydro-2-benzosiline fragments [54-56]. The deformation of heterocycle is characteristic for
all these structures. The angle described this deformation in compound 3 Si-O-C consists
124.67˚, in 6,6-dimethyl-7-phenyl-5,6-dihydroindolo[1,2-a][1,3]benzazasiline Si-C-C is 109.56
[53], in 2,2-diphenyl-2-sila-1,3,4-trihydronaphthalene [54] Si-C-C is 110.57, in 5,5-diphenyl-
1,2,3,4,4a,5,6,10b-octahydro-1,4-methanodibenzo(b,d)siline [55] Si-C-C is 107.85, in (-)-2-(a-
naphthyl)-2-fluoro-2-sila-1,2,3,4-tetrahydronaphthalene [56] Si-C-C is 110.46. Obviously,
oxygen atom plays more significant role in deformation of structural framework in comparison
with carbon.
3.4. The FTIR and DFT study of amide 1 self-association
The investigation of infrared spectra of compound 1 shows that in crystal (KBr)
molecules are fully associated (
ν
NH = 3290 cm-1) whereas in diluted solutions in inert media
NH
(CCl4) they exist as monomer molecules characterized by high-frequency absorption band
ν
at 3434 cm-1. The increasing of concentration of amide 1 in solution provides to appearing new
absorption band at 3393 cm-1 which belongs to self-associates. Spectral shift ∆νNH for
compound 1 is 41cm-1 that lower of that in recently investigated N-(trimethylsilyl)amides [51].
Short spectral shift means weak H-bonding in associates of amide 1. DFT calculations
(B3LYP/6-311+G**) of dimer of compound 1 shows that dimerization energy is 3.18 kcal/mol,
that also much less in comparison with N-(trimethylsilyl)amides dimers [51]. Gas phase

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calculations of molecules 1 lead to significant changes of molecular geometry in comparison
with X-ray geometry. Geometry optimization of compound 1 molecule results in torsion of
amide moiety MeC(O)NH to a plane of benzene ring with angle of 42.89˚ relatively benzene ring
(Fig. 4). Therefore calculations of energy of monomer and dimer molecules of compound 1 were
done using frozen X-ray geometry. Calculated length of H-bond in dimer of compound 1
estimate 2.110 Å that is very close to experimental data 2.111 Å.
Fig. 4. Positon of amide’s fragment relative to benzene ring plane in molecules of compound 1.
Conclusion
The interaction of N-(2-hydroxyphenyl)acetamide with hexamethyldisilazane lead to the
formation of O-trimethylsilyl derivative - N-(2-(trimethylsilyloxy)phenyl)acetamide 1 with good
yield. N-(2-Hydroxyphenyl)acetamide reacts with two equivalents. of Me3SiCl with forming of
mixture of compound 1 and N-[2-(trimethylsilyloxy)pheny])-N-trimethylsilylacetamide 2 with
ratio 1 : 2 = 1 : 0.8. According to X-ray data molecules of compound 1 present in trans-form of
amide. The investigation of structure of compound 1 by X-ray, IR-FTIR and DFT methods
shows that in crystal its molecules are fully associated. The reaction of compound 1 with
ClCH2SiMe2Cl in presence of triethylamine leads to formation of 4-acetyl-2,2-dimethyl-3,4-
dihydro-2H-1,4,2-benzoxazasiline 3 represented as colorless crystals. An extreme broadening
1
signal of methylene protons is exhibited in H NMR spectrum of this compound produced by
rotation of acetyl moiety about C-N bond. Structure of compound 3 was confirmed by X-ray
data.
Acknowledgements
All data were obtained with use the analytical equipment of Baikal Center of collective use of
the SB RAS.

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Highlights
The reaction of N-(2-(trimethylsilyloxy)phenyl)acetamide compound 1 with ClCH2SiMe2Cl in
presence of triethylamine leads to formation of 4-acetyl-2,2-dimethyl-3,4-dihydro-2H-1,4,2-
benzoxazasiline 3 represented as colorless crystals. An extreme broadening signal of methylene
1
protons is exhibited in H NMR spectrum of this compound produced by rotation of acetyl
moiety about C-N bond. Structure of compound 1 and 3 were confirmed by X-ray data.